Glucose-6-phosphate isomerase (phosphoglucose isomerase, PGI; EC 5.3.1.9) catalyzes the reversible aldose-ketose interconversion of glucose-6-phosphate and fructose-6-phosphate, the second step of glycolysis and the corresponding reverse step of gluconeogenesis. The catalytically active form is a cytosolic homodimer. GPI is a classic moonlighting protein; the same polypeptide, when secreted, acts extracellularly as a cytokine and growth factor known historically as neuroleukin (a neurotrophic factor and inducer of immunoglobulin secretion), autocrine motility factor (AMF, an angiogenic factor that stimulates cell and endothelial motility via the cell-surface receptor gp78/AMFR), and maturation factor. Loss-of-function variants cause glucose-6-phosphate isomerase deficiency, an autosomal recessive hereditary nonspherocytic hemolytic anemia sometimes accompanied by neurological impairment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004347 glucose-6-phosphate isomerase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred glucose-6-phosphate isomerase activity. This is the core, well-established molecular function of GPI, directly demonstrated for the human enzyme and conserved across all life. Reason: This is the defining catalytic function of GPI (EC 5.3.1.9), the second enzyme of glycolysis, confirmed for the human protein and consistent across the GPI family. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Isomerase that catalyzes the conversion of alpha-D-glucose-6- PMID:28803808 Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred cytosolic localization, matching the intracellular compartment where the glycolytic/gluconeogenic reaction occurs. Reason: The catalytically active homodimer acts in the cytoplasm/cytosol, consistent with GPI's role in cytosolic glycolysis and gluconeogenesis. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0006094 gluconeogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: GPI catalyzes the reversible G6P to F6P step, which operates in the gluconeogenic direction, making it a core participant in gluconeogenesis. Reason: The reversible isomerase reaction is a committed step of both glycolysis and gluconeogenesis; UniProt explicitly notes the reverse reaction in gluconeogenesis. Supporting Evidence: file:human/GPI/GPI-uniprot.txt and the reverse reaction in gluconeogenesis, within the |
| GO:0006096 glycolytic process | IBA GO_REF:0000033 | ACCEPT | Summary: GPI performs the second step of glycolysis (G6P to F6P) and is a core glycolytic enzyme. Reason: Directly supported; GPI is the second glycolytic enzyme, a core biological process for this gene. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0051156 glucose 6-phosphate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: GPI acts on glucose-6-phosphate as its substrate, so participation in glucose-6-phosphate metabolism follows directly from its catalytic activity. Reason: Consistent with the catalytic activity; glucose-6-phosphate is the direct substrate of the enzyme. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Isomerase that catalyzes the conversion of alpha-D-glucose-6- |
| GO:0048029 monosaccharide binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: GPI binds its phosphorylated monosaccharide substrates (glucose-6-phosphate, fructose-6-phosphate). This binding is a mechanistic prerequisite of catalysis rather than an independent function. Reason: Substrate binding is subsumed by the catalytic activity annotation; retained but not a distinct core function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt ligand="D-glucose 6-phosphate" |
| GO:0004347 glucose-6-phosphate isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (multiple IEA methods, incl. Rhea RHEA:11816 and EC 5.3.1.9) of the core glucose-6-phosphate isomerase activity. Reason: Redundant with the experimentally supported core MF annotation; the electronic mapping to EC 5.3.1.9 / RHEA:11816 is correct. Supporting Evidence: file:human/GPI/GPI-uniprot.txt EC=5.3.1.9 |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic mapping from the UniProt Secreted subcellular-location keyword. GPI is genuinely secreted and functions extracellularly as the AMF/neuroleukin cytokine, but this is a moonlighting pool, not the core cytosolic enzyme. Reason: Correct for the secreted moonlighting form (autocrine motility factor), but peripheral to GPI's core glycolytic role. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381}. Secreted |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping from the UniProt Cytoplasm subcellular-location keyword, consistent with the compartment of the core glycolytic reaction. Reason: Correct; GPI is a cytoplasmic/cytosolic enzyme. The more specific cytosol term is captured elsewhere. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0006094 gluconeogenesis | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of gluconeogenesis, redundant with the IBA annotation. Reason: Correct; GPI's reversible reaction operates in gluconeogenesis. Supporting Evidence: file:human/GPI/GPI-uniprot.txt and the reverse reaction in gluconeogenesis, within the |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of glycolytic process, redundant with the IBA annotation. Reason: Correct core biological process for GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0016853 isomerase activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA electronic annotation to the broad parent term isomerase activity. Reason: This is the generic grandparent of the specific glucose-6-phosphate isomerase activity that is already annotated; the specific term should be preferred. Supporting Evidence: file:human/GPI/GPI-uniprot.txt EC=5.3.1.9 |
| GO:0047938 glucose-6-phosphate 1-epimerase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea-based electronic mapping (RHEA:16249) to a G6P anomerase/epimerase activity, interconverting the alpha and beta anomers of glucose-6-phosphate. UniProt records this anomerase activity only by similarity for the human enzyme. Reason: Plausible ancillary anomerase side-activity supported by similarity, but not the core physiological function and not experimentally demonstrated in human. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Reaction=alpha-D-glucose 6-phosphate = beta-D-glucose 6-phosphate |
| GO:0097367 carbohydrate derivative binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO electronic assignment of the broad term carbohydrate derivative binding, reflecting binding of the phosphosugar substrates. Reason: Uninformatively broad; the specific monosaccharide/substrate binding is already implied by the catalytic activity annotation. Supporting Evidence: file:human/GPI/GPI-uniprot.txt ligand="D-glucose 6-phosphate" |
| GO:1901135 carbohydrate derivative metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO electronic assignment of the broad process carbohydrate derivative metabolic process. Reason: Overly general; the specific glycolytic/gluconeogenic and glucose-6-phosphate metabolic processes are already annotated. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | MARK AS OVER ANNOTATED | Summary: IntAct-derived protein binding annotation from a high-throughput mitochondrial interactome screen, capturing a physical interaction of GPI with TAMM41 (Q96BW9). Reason: Bare protein binding is uninformative about molecular function; the interaction derives from a large-scale mitochondrial affinity-enrichment screen and does not define a specific function for GPI. Per curation policy, this is marked over-annotated rather than removed. Supporting Evidence: PMID:27499296 we assessed condition-specific protein-protein |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology-based electronic assignment of cytosol, consistent with the compartment of the active enzyme. Reason: Correct; the active GPI homodimer functions in the cytosol. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology-transferred plasma membrane localization from the mouse ortholog. GPI is a soluble cytosolic/secreted protein without a transmembrane domain; any plasma-membrane association is peripheral (e.g. secreted AMF binding surface gp78). Reason: GPI is not an integral plasma membrane protein; the term over-states a transient/peripheral association and is an over-propagated ortholog transfer. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0006002 fructose 6-phosphate metabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Fructose-6-phosphate is the direct product/substrate of the GPI reaction, so participation in fructose-6-phosphate metabolism follows from its catalytic activity. Reason: Correct; fructose-6-phosphate is directly interconverted with glucose-6-phosphate by GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt to beta-D-fructose-6-phosphate |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from the rat ortholog of a phenotype/context association (learning or memory), not a molecular function of GPI. Reason: Over-propagated organismal-phenotype IEA transferred from rat; not part of GPI's core enzymatic function and not established for the human protein. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0007611; P:learning or memory; IEA:Ensembl |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a hormone-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0032355; P:response to estradiol; IEA:Ensembl |
| GO:0032570 response to progesterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a hormone-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0032570; P:response to progesterone; IEA:Ensembl |
| GO:0033574 response to testosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a hormone-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0033574; P:response to testosterone; IEA:Ensembl |
| GO:0035902 response to immobilization stress | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a stress-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0035902; P:response to immobilization stress; IEA:Ensembl |
| GO:0035994 response to muscle stretch | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a physiological-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0035994; P:response to muscle stretch; IEA:Ensembl |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of an anti-apoptotic association, possibly reflecting the pro-survival neurotrophic/neuroleukin moonlighting role. Reason: Over-propagated ortholog-transfer IEA; if real it relates to the secreted cytokine moonlighting activity rather than the core enzyme, and is not established for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl |
| GO:0046686 response to cadmium ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from rat of a chemical-response context association. Reason: Over-propagated context IEA transferred from the rat ortholog; not a core function and not demonstrated for human GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt GO:0046686; P:response to cadmium ion; IEA:Ensembl |
| GO:0048029 monosaccharide binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl orthology-based electronic assignment of monosaccharide binding, redundant with the IBA monosaccharide-binding annotation. Reason: Substrate binding subsumed by the catalytic activity; retained but not a distinct core function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt ligand="D-glucose 6-phosphate" |
| GO:0051156 glucose 6-phosphate metabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of glucose-6-phosphate metabolic process, redundant with the IBA/IDA annotations. Reason: Correct; glucose-6-phosphate is the direct substrate of GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Isomerase that catalyzes the conversion of alpha-D-glucose-6- |
| GO:0060170 ciliary membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl orthology transfer from mouse of a ciliary membrane localization. GPI is a soluble cytosolic/secreted enzyme with no evidence for a ciliary-membrane role in human. Reason: Implausible, over-propagated ortholog-transfer IEA for a soluble glycolytic enzyme lacking membrane-targeting features. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0061621 canonical glycolysis | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl orthology-based electronic assignment of canonical glycolysis, the specific glycolytic pathway in which GPI catalyzes the second step. Reason: Correct and appropriately specific core process for GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0006094 gluconeogenesis | TAS Reactome:R-HSA-70263 | ACCEPT | Summary: Reactome traceable assertion (Gluconeogenesis pathway) that GPI participates in gluconeogenesis via the reversible G6P to F6P step. Reason: Correct core process; consistent with the reversible isomerase reaction. Supporting Evidence: file:human/GPI/GPI-uniprot.txt and the reverse reaction in gluconeogenesis, within the |
| GO:0061621 canonical glycolysis | TAS Reactome:R-HSA-70171 | ACCEPT | Summary: Reactome traceable assertion (Glycolysis pathway) placing GPI in canonical glycolysis. Reason: Correct and appropriately specific core process for GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt the second step in |
| GO:0004347 glucose-6-phosphate isomerase activity | EXP PMID:13538944 Enzymes of the human erythrocyte. IV. Phosphoglucose isomera... | ACCEPT | Summary: Experimental characterization of purified human erythrocyte phosphoglucose isomerase, establishing the core glucose-6-phosphate isomerase activity. Reason: Classic biochemical evidence for the enzyme's core catalytic function in human tissue. Supporting Evidence: PMID:13538944 Enzymes of the human erythrocyte. IV. Phosphoglucose isomerase, purification and properties. |
| GO:0004347 glucose-6-phosphate isomerase activity | TAS Reactome:R-HSA-70471 | ACCEPT | Summary: Reactome traceable assertion (GPI dimer isomerizes G6P) for the core catalytic activity. Reason: Correct core molecular function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Isomerase that catalyzes the conversion of alpha-D-glucose-6- |
| GO:0051156 glucose 6-phosphate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer (from yeast/ortholog) of glucose-6-phosphate metabolic process, redundant with the IBA/IDA annotations. Reason: Correct; glucose-6-phosphate is the direct substrate of GPI. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Isomerase that catalyzes the conversion of alpha-D-glucose-6- |
| GO:0005576 extracellular region | EXP PMID:11437381 Tumor autocrine motility factor is an angiogenic factor that... | KEEP AS NON CORE | Summary: Experimental evidence that GPI/AMF is secreted and acts extracellularly as an angiogenic autocrine motility factor stimulating endothelial cell motility. Reason: Correct for the secreted moonlighting form (AMF), but extracellular localization is peripheral to GPI's core cytosolic glycolytic function. Supporting Evidence: PMID:11437381 AMF stimulated in vitro motility of human umbilical vein |
| GO:0005737 cytoplasm | EXP PMID:11437381 Tumor autocrine motility factor is an angiogenic factor that... | ACCEPT | Summary: Experimental subcellular localization placing GPI in the cytoplasm, the compartment of its core glycolytic activity. Reason: Correct; GPI is a cytoplasmic/cytosolic enzyme. Supporting Evidence: PMID:11437381 Tumor autocrine motility factor is an angiogenic factor that stimulates |
| GO:0047938 glucose-6-phosphate 1-epimerase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity transfer of an anomerase/epimerase activity on glucose-6-phosphate; UniProt records this activity only by similarity for human GPI. Reason: Plausible ancillary anomerase side-activity supported by similarity, but not the core physiological function and not experimentally demonstrated in human. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Reaction=alpha-D-glucose 6-phosphate = beta-D-glucose 6-phosphate |
| GO:0016857 racemase and epimerase activity, acting on carbohydrates and derivatives | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence-similarity transfer to the broad parent term for carbohydrate racemase/epimerase activity, reflecting the by-similarity C2-epimerase/anomerase side reactions. Reason: Overly broad grandparent term; the specific (by-similarity) glucose-6-phosphate epimerase activity is already annotated separately. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Glucose-6-phosphate C2-epimerase |
| GO:0004347 glucose-6-phosphate isomerase activity | IDA PMID:28803808 Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causin... | ACCEPT | Summary: Direct assay of GPI catalytic activity in patients with GPI deficiency, where pathogenic variants reduce residual enzyme activity, confirming the core isomerase function. Reason: Direct experimental support for the core molecular function in the human protein; residual GPI activity was measured in patient erythrocytes. Supporting Evidence: PMID:28803808 lost approximately 89% of their GPI activity |
| GO:0051156 glucose 6-phosphate metabolic process | IDA PMID:28803808 Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causin... | ACCEPT | Summary: Direct evidence that GPI acts in glucose-6-phosphate metabolism, from patient enzyme-activity measurements in GPI deficiency. Reason: Correct; glucose-6-phosphate is the direct substrate of GPI. Supporting Evidence: PMID:28803808 is the second most common red blood |
| GO:0010595 positive regulation of endothelial cell migration | IDA PMID:1649192 Purification of human tumor cell autocrine motility factor a... | KEEP AS NON CORE | Summary: Purified GPI/AMF stimulates cell migration and, via its receptor gp78, promotes motility; a moonlighting cytokine activity of the secreted protein. Reason: A genuine moonlighting activity of secreted GPI (autocrine motility factor), but distinct from its core glycolytic enzyme role. Supporting Evidence: PMID:1649192 Purified AMF stimulated HT-1080 cell PMID:11437381 AMF stimulated in vitro motility of human umbilical vein |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Reactome traceable assertion placing GPI in the extracellular region via exocytosis of secretory granule lumen proteins (neutrophil degranulation). Reason: Consistent with the secreted moonlighting pool of GPI, but peripheral to the core cytosolic enzyme function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381}. Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome traceable assertion placing GPI in the extracellular region via exocytosis of ficolin-rich granule lumen proteins. Reason: Consistent with the secreted moonlighting pool of GPI, but peripheral to the core cytosolic enzyme function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381}. Secreted |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Reactome traceable assertion localizing GPI to the secretory granule lumen in the context of neutrophil degranulation. Reason: Reflects the granule/secretion route of the moonlighting extracellular pool, not the core cytosolic function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381}. Secreted |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome traceable assertion localizing GPI to the ficolin-1-rich granule lumen (neutrophil degranulation pathway). Reason: Reflects the granule/secretion route of the moonlighting extracellular pool, not the core cytosolic function. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381}. Secreted |
| GO:0002639 positive regulation of immunoglobulin production | IDA PMID:3020690 Neuroleukin: a lymphokine product of lectin-stimulated T cel... | KEEP AS NON CORE | Summary: GPI/neuroleukin, secreted by lectin-stimulated T cells, induces immunoglobulin secretion by human peripheral blood mononuclear cells; a moonlighting cytokine activity. Reason: A genuine moonlighting cytokine function of secreted GPI (neuroleukin), distinct from its core glycolytic enzyme role. Supporting Evidence: PMID:3020690 Neuroleukin is a lymphokine product of lectin-stimulated T cells that induces immunoglobulin secretion by cultured human peripheral blood mononuclear cells. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:24810856 Polyubiquitylation of AMF requires cooperation between the g... | KEEP AS NON CORE | Summary: GPI/AMF binds directly to the cytoplasmic domain of the ubiquitin ligase gp78/AMFR (Q9UKV5) and is a substrate for its (E4-like) polyubiquitylation. Reason: A specific, experimentally demonstrated interaction of GPI/AMF with the gp78 ubiquitin ligase, informative but part of the moonlighting AMF biology rather than the core enzyme function. Supporting Evidence: PMID:24810856 We found that AMF indeed directly interacted with the cytoplasmic domain of gp78 |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: GPI detected by high-throughput proteomics in exosomes from expressed prostatic secretions in urine. Reason: Consistent with the secreted/extracellular moonlighting pool detected in a large-scale exosome proteomic survey; peripheral to the core function. Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: GPI detected in a high-throughput NK-cell membrane proteome; the study itself notes many identified species are only transiently associated with membranes. Reason: The generic membrane term derives from a large-scale membrane-proteome survey in which soluble proteins co-purify; GPI has no transmembrane domain and this does not reflect a stable membrane localization. Supporting Evidence: PMID:19946888 species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: GPI detected by high-throughput proteomics in human parotid gland exosomes. Reason: Consistent with the secreted/extracellular moonlighting pool detected in a large-scale exosome proteomic survey; peripheral to the core function. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: GPI detected by high-throughput proteomics in human urinary exosomes. Reason: Consistent with the secreted/extracellular moonlighting pool detected in a large-scale exosome proteomic survey; peripheral to the core function. Supporting Evidence: PMID:19056867 Large-scale 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: GPI detected by high-throughput proteomics in B-cell exosomes. Reason: Consistent with the secreted/extracellular moonlighting pool detected in a large-scale exosome proteomic survey; peripheral to the core function. Supporting Evidence: PMID:20458337 MHC class II-associated proteins in B-cell exosomes |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70471 | ACCEPT | Summary: Reactome traceable assertion localizing GPI to the cytosol (GPI dimer isomerizes G6P reaction). Reason: Correct; the active enzyme functions in the cytosol. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70475 | ACCEPT | Summary: Reactome traceable assertion localizing GPI to the cytosol (GPI dimer isomerizes Fru(6)P to G6P reaction). Reason: Correct; the active enzyme functions in the cytosol. Supporting Evidence: file:human/GPI/GPI-uniprot.txt Cytoplasm {ECO:0000269|PubMed:11437381} |
| GO:0005975 carbohydrate metabolic process | NAS PMID:8575767 Human glucose phosphate isomerase: exon mapping and gene str... | MARK AS OVER ANNOTATED | Summary: Non-traceable author statement of carbohydrate metabolic process, from a paper on GPI exon/gene structure. Reason: Overly general parent term; the specific glycolytic/gluconeogenic and glucose-6-phosphate metabolic processes are already annotated. Supporting Evidence: PMID:8575767 The structure of the gene for human glucose phosphate isomerase (GPI) has been determined. |
| GO:0006959 humoral immune response | TAS PMID:3020690 Neuroleukin: a lymphokine product of lectin-stimulated T cel... | KEEP AS NON CORE | Summary: Traceable assertion based on GPI/neuroleukin inducing immunoglobulin secretion, contributing to the humoral immune response; a moonlighting cytokine activity. Reason: Genuine moonlighting immunological activity of secreted GPI (neuroleukin), distinct from its core glycolytic function. Supporting Evidence: PMID:3020690 Neuroleukin is a lymphokine product of lectin-stimulated T cells that induces |
| GO:0007599 hemostasis | TAS PMID:7435496 The first stable variant of erythrocyte glucose-phosphate is... | MARK AS OVER ANNOTATED | Summary: Traceable assertion of hemostasis citing a report of a stable GPI variant associated with severe hemolytic anemia. The cited paper concerns a hemolytic-anemia enzyme variant, not blood clotting/hemostasis. Reason: The supporting reference describes a GPI-deficiency hemolytic-anemia variant and its altered kinetics, not a role in hemostasis; the term appears to be a mis-mapping and does not reflect a GPI function. Supporting Evidence: PMID:7435496 A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described. |
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Download this section (compressed HTML)Q: Is the by-similarity anomerase/C2-epimerase activity of human GPI physiologically significant, or an in vitro artifact of the isomerase mechanism?
Q: To what extent does the secreted neuroleukin/AMF cytokine pool contribute to human physiology (immunity, angiogenesis, neurotrophic support) versus being predominantly a cancer-associated moonlighting activity?
Experiment: Quantify the secreted (monomeric AMF/neuroleukin) versus cytosolic (dimeric enzyme) pools of GPI across cell types and correlate secretion with CK2 phosphorylation at Ser-185.
Experiment: Structure-function analysis of CNSHA4 disease variants to dissect effects on catalytic activity, dimer stability, and cytokine (gp78-binding) activity.
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