Epo encodes mouse erythropoietin, a secreted glycoprotein cytokine hormone of the EPO/TPO family. The mature ligand is produced mainly by kidney in adult mammals and liver in fetal or neonatal contexts, is induced by hypoxia-regulated HIF signaling, and circulates to erythroid progenitors where it binds EPOR and activates JAK2/STAT and MAPK-linked signaling. The core supported function is endocrine receptor-ligand control of definitive erythropoiesis: survival, proliferation, differentiation, maturation, and hemoglobinization of erythroid cells. Reported effects on neural, immune, cardiac-development and cell-surface processes are downstream consequences of that signalling in particular tissue contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005128 erythropoietin receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Epo directly functions as the ligand for the erythropoietin receptor. Reason: EPOR binding is the precise molecular function that initiates Epo signaling and erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. Reactome:R-MMU-9006326 Reactome models mouse Epo binding the Epor:JAK2-containing receptor complex as the initiating event in erythropoietin signaling. |
| GO:0005179 hormone activity | IBA GO_REF:0000033 | ACCEPT | Summary: Epo is a secreted endocrine hormone regulating erythrocyte mass. Reason: Hormone activity accurately captures the circulating endocrine role of Epo, though receptor binding is the more precise MF. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. |
| GO:0030218 erythrocyte differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: Epo supports erythrocyte differentiation, especially definitive/stress erythropoiesis. Reason: Erythroid differentiation is a direct biological outcome of Epo/EPOR signaling and is central to the gene function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0030295 protein kinase activator activity | IBA GO_REF:0000033 | MODIFY | Summary: Epo activates kinase cascades indirectly through EPOR, but protein kinase activator activity is not the best direct MF term. Reason: The ligand directly binds EPOR; kinase activation is a downstream BP consequence of receptor signaling rather than an independent protein kinase activator molecular activity. Positive regulation of protein kinase activity remains valid as pathway context, but it is a BP term and should not be proposed as a replacement for this MF annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:95407 · mouse Epo (the review target itself) SUPPORTS TRANSFER The target's own MGI record is the IBD seed, which is the expected marker that experimental grounding exists on Epo itself and helped place the ancestral call; the IBA then adds that the function is inherited rather than mouse-specific. The propagation is therefore sound and the fault is in the term: EPO is a secreted cytokine that binds and dimerises EPOR, and the JAK2 activation that follows is a downstream consequence of receptor engagement, not an intrinsic protein kinase activator activity of the ligand. Proposed replacements: erythropoietin receptor binding Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0038162 erythropoietin-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Epo initiates the erythropoietin-mediated signaling pathway by binding EPOR. Reason: This is the pathway named for the ligand and is the correct BP context for downstream JAK2/STAT, PI3K, RAS, and ERK events. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0097696 cell surface receptor signaling pathway via STAT | IBA GO_REF:0000033 | ACCEPT | Summary: Epo/EPOR signaling activates STAT-family transcriptional signaling downstream of JAK2. Reason: STAT signaling is a canonical immediate branch of Epo receptor activation and is part of the core pathway. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0005125 cytokine activity | IBA GO_REF:0000033 | ACCEPT | Summary: Epo is a hematopoietic cytokine ligand acting through EPOR. Reason: Cytokine activity is supported by UniProt, Falcon, and Epo-dependent erythroid survival evidence. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 proliferation and survival of erythroid cells in response to Epo |
| GO:0005615 extracellular space | IBA GO_REF:0000033 | ACCEPT | Summary: Epo is secreted and acts in the extracellular space. Reason: Extracellular space is the appropriate core location for the circulating ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005128 erythropoietin receptor binding | IEA GO_REF:0000120 | ACCEPT | Summary: Epo directly functions as the ligand for the erythropoietin receptor. Reason: EPOR binding is the precise molecular function that initiates Epo signaling and erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. Reactome:R-MMU-9006326 Reactome models mouse Epo binding the Epor:JAK2-containing receptor complex as the initiating event in erythropoietin signaling. |
| GO:0005179 hormone activity | IEA GO_REF:0000120 | ACCEPT | Summary: Epo is a secreted endocrine hormone regulating erythrocyte mass. Reason: Hormone activity accurately captures the circulating endocrine role of Epo, though receptor binding is the more precise MF. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0006950 response to stress | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Response to stress is too broad for the supported Epo function. Reason: The stress connection is better captured by hypoxia-regulated Epo production and erythropoietic response rather than a generic response-to-stress annotation. Supporting Evidence: PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse PMID:17981124 embryos show severe fetal anemia stemming from deficient erythropoietin (Epo) file:mouse/Epo/Epo-deep-research-falcon.md Falcon emphasizes renal Epo induction by hypoxia through HIF signaling and renal EPO-producing interstitial cells. |
| GO:0043249 erythrocyte maturation | IEA GO_REF:0000043 | ACCEPT | Summary: Epo promotes erythrocyte maturation as part of its erythropoietic hormone function. Reason: Maturation is consistent with UniProt keyword evidence and the Falcon synthesis of Epo as the principal erythroid growth and maturation factor. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Generic RNA polymerase II transcription regulation is downstream of receptor signaling and too broad for Epo. Reason: Epo can induce transcriptional programs through EPOR/JAK/STAT, but the appropriate annotation is erythropoietin-mediated signaling or specific downstream erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0005125 cytokine activity | ISO GO_REF:0000119 | ACCEPT | Summary: Epo is a hematopoietic cytokine ligand acting through EPOR. Reason: Cytokine activity is supported by UniProt, Falcon, and Epo-dependent erythroid survival evidence. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 proliferation and survival of erythroid cells in response to Epo |
| GO:0005128 erythropoietin receptor binding | ISO GO_REF:0000119 | ACCEPT | Summary: Epo directly functions as the ligand for the erythropoietin receptor. Reason: EPOR binding is the precise molecular function that initiates Epo signaling and erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. Reactome:R-MMU-9006326 Reactome models mouse Epo binding the Epor:JAK2-containing receptor complex as the initiating event in erythropoietin signaling. |
| GO:0005179 hormone activity | ISO GO_REF:0000119 | ACCEPT | Summary: Epo is a secreted endocrine hormone regulating erythrocyte mass. Reason: Hormone activity accurately captures the circulating endocrine role of Epo, though receptor binding is the more precise MF. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. |
| GO:0005615 extracellular space | ISO GO_REF:0000119 | ACCEPT | Summary: Epo is secreted and acts in the extracellular space. Reason: Extracellular space is the appropriate core location for the circulating ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Epo promotes proliferation of erythroid progenitors, but the term is broader than the core ligand function. Reason: The annotation is directionally correct as an erythroid outcome but should be interpreted in the erythropoietic context, not as generic proliferation across cell types. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0009986 cell surface | ISO GO_REF:0000119 | REMOVE | Summary: Cell surface localization is not supported for Epo as a secreted ligand. Reason: Epo acts on cell-surface EPOR after secretion, but the Epo protein itself is not a membrane or cell-surface resident protein in UniProt or Falcon. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0010523 negative regulation of calcium ion transport into cytosol | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: negative regulation of calcium ion transport into cytosol is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0030218 erythrocyte differentiation | ISO GO_REF:0000119 | ACCEPT | Summary: Epo supports erythrocyte differentiation, especially definitive/stress erythropoiesis. Reason: Erythroid differentiation is a direct biological outcome of Epo/EPOR signaling and is central to the gene function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0038162 erythropoietin-mediated signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Epo initiates the erythropoietin-mediated signaling pathway by binding EPOR. Reason: This is the pathway named for the ligand and is the correct BP context for downstream JAK2/STAT, PI3K, RAS, and ERK events. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Generic RNA polymerase II transcription regulation is downstream of receptor signaling and too broad for Epo. Reason: Epo can induce transcriptional programs through EPOR/JAK/STAT, but the appropriate annotation is erythropoietin-mediated signaling or specific downstream erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0046579 positive regulation of Ras protein signal transduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: RAS activation is a recognized downstream branch of Epo signaling. Reason: This captures a downstream pathway module, whereas the core function remains EPOR ligand activity and erythropoietin-mediated signaling. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. Reactome:R-MMU-9029152 Reactome models Epo:Epor:JAK2-linked complexes mediating GDP-GTP exchange on Ras. |
| GO:0071474 cellular hyperosmotic response | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: cellular hyperosmotic response is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0097696 cell surface receptor signaling pathway via STAT | ISO GO_REF:0000119 | ACCEPT | Summary: Epo/EPOR signaling activates STAT-family transcriptional signaling downstream of JAK2. Reason: STAT signaling is a canonical immediate branch of Epo receptor activation and is part of the core pathway. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:1902219 negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:1902251 negative regulation of erythrocyte apoptotic process | ISO GO_REF:0000119 | ACCEPT | Summary: Epo prevents apoptosis of erythroid cells during erythropoiesis. Reason: Erythroid survival is a core biological effect of Epo/EPOR signaling. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic RNA polymerase II transcription regulation is downstream of receptor signaling and too broad for Epo. Reason: Epo can induce transcriptional programs through EPOR/JAK/STAT, but the appropriate annotation is erythropoietin-mediated signaling or specific downstream erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epo expression and systemic Epo response are hypoxia-regulated. Reason: Hypoxia is a major upstream regulator and physiological context for Epo production, but the gene product function is the secreted hormone signal. Supporting Evidence: PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse PMID:17981124 embryos show severe fetal anemia stemming from deficient erythropoietin (Epo) file:mouse/Epo/Epo-deep-research-falcon.md Falcon emphasizes renal Epo induction by hypoxia through HIF signaling and renal EPO-producing interstitial cells. |
| GO:0005125 cytokine activity | IEA GO_REF:0000107 | ACCEPT | Summary: Epo is a hematopoietic cytokine ligand acting through EPOR. Reason: Cytokine activity is supported by UniProt, Falcon, and Epo-dependent erythroid survival evidence. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 proliferation and survival of erythroid cells in response to Epo |
| GO:0005615 extracellular space | IEA GO_REF:0000120 | ACCEPT | Summary: Epo is secreted and acts in the extracellular space. Reason: Extracellular space is the appropriate core location for the circulating ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0006953 acute-phase response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: acute-phase response is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to nutrient is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Epo promotes proliferation of erythroid progenitors, but the term is broader than the core ligand function. Reason: The annotation is directionally correct as an erythroid outcome but should be interpreted in the erythropoietic context, not as generic proliferation across cell types. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0009651 response to salt stress | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to salt stress is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | REMOVE | Summary: Cell surface localization is not supported for Epo as a secreted ligand. Reason: Epo acts on cell-surface EPOR after secretion, but the Epo protein itself is not a membrane or cell-surface resident protein in UniProt or Falcon. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0010523 negative regulation of calcium ion transport into cytosol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: negative regulation of calcium ion transport into cytosol is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: positive regulation of neuron projection development reflects non-erythroid neurotrophic contexts rather than the conserved core Epo function. Reason: Falcon notes non-erythropoietic roles can occur in specific contexts, but the annotation is automated/orthology-derived and not supported as a primary mouse Epo function here. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0030218 erythrocyte differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: Epo supports erythrocyte differentiation, especially definitive/stress erythropoiesis. Reason: Erythroid differentiation is a direct biological outcome of Epo/EPOR signaling and is central to the gene function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to lipopolysaccharide is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0033189 response to vitamin A | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to vitamin A is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0033574 response to testosterone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to testosterone is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0038162 erythropoietin-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Epo initiates the erythropoietin-mediated signaling pathway by binding EPOR. Reason: This is the pathway named for the ligand and is the correct BP context for downstream JAK2/STAT, PI3K, RAS, and ERK events. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0042104 positive regulation of activated T cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Activated T cell proliferation is not supported as a core mouse Epo function in the reviewed evidence. Reason: This transferred immune term is outside the canonical EPOR ligand role in erythropoiesis and lacks direct support in UniProt/Falcon/local publications. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0043627 response to estrogen | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to estrogen is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0044297 cell body | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cell body localization is not a supported core location for mouse Epo. Reason: The core location is extracellular/secreted; cell body appears to be transferred from non-canonical contexts and should not be treated as a general Epo localization. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0045666 positive regulation of neuron differentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: positive regulation of neuron differentiation reflects non-erythroid neurotrophic contexts rather than the conserved core Epo function. Reason: Falcon notes non-erythropoietic roles can occur in specific contexts, but the annotation is automated/orthology-derived and not supported as a primary mouse Epo function here. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic RNA polymerase II transcription regulation is downstream of receptor signaling and too broad for Epo. Reason: Epo can induce transcriptional programs through EPOR/JAK/STAT, but the appropriate annotation is erythropoietin-mediated signaling or specific downstream erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0046579 positive regulation of Ras protein signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAS activation is a recognized downstream branch of Epo signaling. Reason: This captures a downstream pathway module, whereas the core function remains EPOR ligand activity and erythropoietin-mediated signaling. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. Reactome:R-MMU-9029152 Reactome models Epo:Epor:JAK2-linked complexes mediating GDP-GTP exchange on Ras. |
| GO:0048678 response to axon injury | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to axon injury is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0051602 response to electrical stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to electrical stimulus is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0055093 response to hyperoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to hyperoxia is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ERK1/2 activation can occur downstream of Epo signaling but is not the primary annotation level for Epo. Reason: MAPK/ERK is a downstream branch of Epo/EPOR signaling, best retained as non-core rather than as the defining function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0070555 response to interleukin-1 | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to interleukin-1 is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0071474 cellular hyperosmotic response | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: cellular hyperosmotic response is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0071548 response to dexamethasone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: response to dexamethasone is a broad stimulus-response annotation transferred from automated evidence. Reason: The review evidence supports hypoxia-regulated Epo production and erythropoietic signaling, not this broad stimulus-response term as an Epo function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0097696 cell surface receptor signaling pathway via STAT | IEA GO_REF:0000107 | ACCEPT | Summary: Epo/EPOR signaling activates STAT-family transcriptional signaling downstream of JAK2. Reason: STAT signaling is a canonical immediate branch of Epo receptor activation and is part of the core pathway. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:1902219 negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress is an osmotic/calcium-stress transfer that is not part of the core mouse Epo function. Reason: These annotations likely derive from context-specific non-erythroid or cellular-stress experiments in other species; they are not supported by the mouse UniProt/Falcon synthesis as primary Epo biology. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:1902251 negative regulation of erythrocyte apoptotic process | IEA GO_REF:0000107 | ACCEPT | Summary: Epo prevents apoptosis of erythroid cells during erythropoiesis. Reason: Erythroid survival is a core biological effect of Epo/EPOR signaling. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0005615 extracellular space | ISO GO_REF:0000096 | ACCEPT | Summary: Epo is secreted and acts in the extracellular space. Reason: Extracellular space is the appropriate core location for the circulating ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Epo promotes proliferation of erythroid progenitors, but the term is broader than the core ligand function. Reason: The annotation is directionally correct as an erythroid outcome but should be interpreted in the erythropoietic context, not as generic proliferation across cell types. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0010976 positive regulation of neuron projection development | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of neuron projection development reflects non-erythroid neurotrophic contexts rather than the conserved core Epo function. Reason: Falcon notes non-erythropoietic roles can occur in specific contexts, but the annotation is automated/orthology-derived and not supported as a primary mouse Epo function here. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0042104 positive regulation of activated T cell proliferation | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Activated T cell proliferation is not supported as a core mouse Epo function in the reviewed evidence. Reason: This transferred immune term is outside the canonical EPOR ligand role in erythropoiesis and lacks direct support in UniProt/Falcon/local publications. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0044297 cell body | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Cell body localization is not a supported core location for mouse Epo. Reason: The core location is extracellular/secreted; cell body appears to be transferred from non-canonical contexts and should not be treated as a general Epo localization. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0045666 positive regulation of neuron differentiation | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: positive regulation of neuron differentiation reflects non-erythroid neurotrophic contexts rather than the conserved core Epo function. Reason: Falcon notes non-erythropoietic roles can occur in specific contexts, but the annotation is automated/orthology-derived and not supported as a primary mouse Epo function here. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: ERK1/2 activation can occur downstream of Epo signaling but is not the primary annotation level for Epo. Reason: MAPK/ERK is a downstream branch of Epo/EPOR signaling, best retained as non-core rather than as the defining function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Proteasome-mediated ubiquitin-dependent protein catabolism is not a supported Epo function. Reason: This appears to be an indirect transferred pathway context, not a process performed or directly controlled by the secreted Epo ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt The UniProt function statement centers Epo on EPOR binding, JAK2 activation, erythrocyte proliferation and differentiation, and secreted localization. file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies the best-supported function as secreted endocrine EPOR ligand activity in definitive erythropoiesis, while non-erythroid response and development terms are context-specific or less directly supported. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9006326 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9006327 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9006329 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9012652 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9012653 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9012656 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9027266 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9027268 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9027429 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9027436 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9029146 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9029147 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9029152 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9029162 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9030346 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9030353 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-9032476 | ACCEPT | Summary: Epo is an extracellular secreted ligand. Reason: Extracellular region is correct, although extracellular space is the more specific location used for the core function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
| GO:0005128 erythropoietin receptor binding | ISS GO_REF:0000024 | ACCEPT | Summary: Epo directly functions as the ligand for the erythropoietin receptor. Reason: EPOR binding is the precise molecular function that initiates Epo signaling and erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. Reactome:R-MMU-9006326 Reactome models mouse Epo binding the Epor:JAK2-containing receptor complex as the initiating event in erythropoietin signaling. |
| GO:0038162 erythropoietin-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Epo initiates the erythropoietin-mediated signaling pathway by binding EPOR. Reason: This is the pathway named for the ligand and is the correct BP context for downstream JAK2/STAT, PI3K, RAS, and ERK events. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0033033 negative regulation of myeloid cell apoptotic process | IDA PMID:17981124 SUMO-specific protease 1 is essential for stabilization of H... | MODIFY | Summary: The SENP1/HIF paper supports deficient Epo production causing fetal anemia, not broad myeloid apoptosis as a direct Epo annotation. Reason: The defensible Epo terms are erythroid differentiation and negative regulation of erythrocyte apoptosis, not broad myeloid apoptosis. Proposed replacements: erythrocyte differentiation negative regulation of erythrocyte apoptotic process Supporting Evidence: PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse PMID:17981124 embryos show severe fetal anemia stemming from deficient erythropoietin (Epo) file:mouse/Epo/Epo-deep-research-falcon.md Falcon emphasizes renal Epo induction by hypoxia through HIF signaling and renal EPO-producing interstitial cells. file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | MODIFY | Summary: Epo does not catalyze peptidyl-serine phosphorylation; it stimulates kinases that phosphorylate substrates such as Bad. Reason: PMID:21095239 attributes Bad phosphorylation to Epo-activated JNK1, not to Epo as an enzyme. The correct curation is positive regulation of kinase activity and erythroid cell survival. Proposed replacements: positive regulation of protein kinase activity negative regulation of erythrocyte apoptotic process Supporting Evidence: PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-uniprot.txt Binds to EPOR leading to EPOR dimerization and JAK2 activation. |
| GO:0030295 protein kinase activator activity | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | MODIFY | Summary: Epo activates kinase cascades indirectly through EPOR, but protein kinase activator activity is not the best direct MF term. Reason: The ligand directly binds EPOR; kinase activation is a downstream BP consequence of receptor signaling rather than an independent protein kinase activator molecular activity. Positive regulation of protein kinase activity remains valid as pathway context, but it is a BP term and should not be proposed as a replacement for this MF annotation. Proposed replacements: erythropoietin receptor binding Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | MODIFY | Summary: Epo has anti-apoptotic effects, but the broad apoptotic-process term should be narrowed to erythroid survival where supported. Reason: The strongest supported context is negative regulation of apoptosis in Epo-dependent erythroid cells, already represented by the more specific erythrocyte apoptotic-process term. Proposed replacements: negative regulation of erythrocyte apoptotic process Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0045860 positive regulation of protein kinase activity | IDA PMID:21095239 Phosphorylation of Bcl-associated death protein (Bad) by ery... | ACCEPT | Summary: Epo signaling positively regulates downstream kinase activity after EPOR engagement. Reason: JAK2, JNK1, and MAPK-family activation are supported downstream of Epo/EPOR signaling. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 file:mouse/Epo/Epo-deep-research-falcon.md Falcon summarizes canonical EPO/EPOR downstream modules as JAK2/STAT5 and RAS/MEK/ERK signaling that coordinate erythroid survival, proliferation, and differentiation. |
| GO:0005128 erythropoietin receptor binding | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | ACCEPT | Summary: Epo directly functions as the ligand for the erythropoietin receptor. Reason: EPOR binding is the precise molecular function that initiates Epo signaling and erythroid outcomes. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. Reactome:R-MMU-9006326 Reactome models mouse Epo binding the Epor:JAK2-containing receptor complex as the initiating event in erythropoietin signaling. |
| GO:0001525 angiogenesis | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | KEEP AS NON CORE | Summary: Angiogenic effects of Epo are plausible but secondary and not the defining mouse Epo function. Reason: The cached source is review-level and Falcon treats non-erythroid tissue effects as context-dependent; retain only as non-core pending stronger direct mouse evidence. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0003007 heart morphogenesis | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | MARK AS OVER ANNOTATED | Summary: heart morphogenesis is too specific and developmental for the evidence available in this review. Reason: The locally cached PMID:20299672 abstract does not provide direct Epo-specific evidence for these heart/coronary/pericardial morphogenesis terms, and Falcon identifies erythropoiesis as the supported core function. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0055008 cardiac muscle tissue morphogenesis | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | MARK AS OVER ANNOTATED | Summary: cardiac muscle tissue morphogenesis is too specific and developmental for the evidence available in this review. Reason: The locally cached PMID:20299672 abstract does not provide direct Epo-specific evidence for these heart/coronary/pericardial morphogenesis terms, and Falcon identifies erythropoiesis as the supported core function. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0055010 ventricular cardiac muscle tissue morphogenesis | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | MARK AS OVER ANNOTATED | Summary: ventricular cardiac muscle tissue morphogenesis is too specific and developmental for the evidence available in this review. Reason: The locally cached PMID:20299672 abstract does not provide direct Epo-specific evidence for these heart/coronary/pericardial morphogenesis terms, and Falcon identifies erythropoiesis as the supported core function. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0060979 vasculogenesis involved in coronary vascular morphogenesis | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | MARK AS OVER ANNOTATED | Summary: vasculogenesis involved in coronary vascular morphogenesis is too specific and developmental for the evidence available in this review. Reason: The locally cached PMID:20299672 abstract does not provide direct Epo-specific evidence for these heart/coronary/pericardial morphogenesis terms, and Falcon identifies erythropoiesis as the supported core function. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0061032 visceral serous pericardium development | TAS PMID:20299672 Epicardial-myocardial signaling directing coronary vasculoge... | MARK AS OVER ANNOTATED | Summary: visceral serous pericardium development is too specific and developmental for the evidence available in this review. Reason: The locally cached PMID:20299672 abstract does not provide direct Epo-specific evidence for these heart/coronary/pericardial morphogenesis terms, and Falcon identifies erythropoiesis as the supported core function. Supporting Evidence: PMID:20299672 mediated in part by secreted growth factors file:mouse/Epo/Epo-deep-research-falcon.md Falcon treats non-erythropoietic tissue outcomes as context-dependent and secondary to the core endocrine erythropoiesis function. |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:17300687 Erythropoietin contributes to implantation: ectopic hemoglob... | MODIFY | Summary: Epo signaling can regulate hemoglobin-related gene expression in decidual cells, but this broad transcription term overstates the direct function. Reason: The PMID:17300687 evidence is better represented as Epo-dependent hemoglobin biosynthesis and decidual survival, downstream of receptor signaling. Proposed replacements: hemoglobin biosynthetic process embryo implantation Supporting Evidence: PMID:17300687 destroyed Hb-containing cells and resulted in apoptosis file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies erythropoietin-mediated erythroid survival and hemoglobin accumulation as a downstream biological outcome of EPOR signaling. |
| GO:0006915 apoptotic process | IDA PMID:17300687 Erythropoietin contributes to implantation: ectopic hemoglob... | MODIFY | Summary: The decidual evidence concerns apoptosis after Epo signaling blockade, so the direction should be anti-apoptotic rather than generic apoptotic process. Reason: Epo signaling supports survival; use negative regulation of apoptotic process instead of the broad apoptotic process term. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:17300687 destroyed Hb-containing cells and resulted in apoptosis file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies erythropoietin-mediated erythroid survival and hemoglobin accumulation as a downstream biological outcome of EPOR signaling. |
| GO:0007566 embryo implantation | IDA PMID:17300687 Erythropoietin contributes to implantation: ectopic hemoglob... | KEEP AS NON CORE | Summary: Epo contributes to mouse implantation through decidual-cell hemoglobin synthesis and survival. Reason: The PMID:17300687 evidence supports this developmental context, but it is not the core conserved function of Epo. Supporting Evidence: PMID:17300687 destroyed Hb-containing cells and resulted in apoptosis file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies erythropoietin-mediated erythroid survival and hemoglobin accumulation as a downstream biological outcome of EPOR signaling. |
| GO:0042541 hemoglobin biosynthetic process | IDA PMID:17300687 Erythropoietin contributes to implantation: ectopic hemoglob... | KEEP AS NON CORE | Summary: Epo signaling promotes hemoglobin synthesis in erythroid and decidual contexts. Reason: Hemoglobin synthesis is a downstream outcome of Epo signaling, not a molecular function of Epo itself. Supporting Evidence: PMID:17300687 destroyed Hb-containing cells and resulted in apoptosis file:mouse/Epo/Epo-deep-research-falcon.md Falcon identifies erythropoietin-mediated erythroid survival and hemoglobin accumulation as a downstream biological outcome of EPOR signaling. file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0030218 erythrocyte differentiation | IDA PMID:15591122 BMP4 and Madh5 regulate the erythroid response to acute anem... | ACCEPT | Summary: Epo supports erythrocyte differentiation, especially definitive/stress erythropoiesis. Reason: Erythroid differentiation is a direct biological outcome of Epo/EPOR signaling and is central to the gene function. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt FUNCTION: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation. file:mouse/Epo/Epo-deep-research-falcon.md Falcon synthesizes mouse Epo as a secreted hypoxia-inducible endocrine cytokine that binds EPOR on erythroid progenitors and activates JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis. file:mouse/Epo/Epo-deep-research-falcon.md Falcon reports that mouse Epo and Epor null mutants have impaired definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5. PMID:15591122 mobilization and differentiation of erythroid progenitors in the adult spleen PMID:21095239 Epo-activated JNK1 phosphorylated Bad at threonine 201 |
| GO:0001666 response to hypoxia | IDA PMID:15016652 Superoxide dismutase-3 promotes full expression of the EPO r... | KEEP AS NON CORE | Summary: Epo expression and systemic Epo response are hypoxia-regulated. Reason: Hypoxia is a major upstream regulator and physiological context for Epo production, but the gene product function is the secreted hormone signal. Supporting Evidence: PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse PMID:17981124 embryos show severe fetal anemia stemming from deficient erythropoietin (Epo) file:mouse/Epo/Epo-deep-research-falcon.md Falcon emphasizes renal Epo induction by hypoxia through HIF signaling and renal EPO-producing interstitial cells. |
| GO:0005615 extracellular space | IDA PMID:15016652 Superoxide dismutase-3 promotes full expression of the EPO r... | ACCEPT | Summary: Epo is secreted and acts in the extracellular space. Reason: Extracellular space is the appropriate core location for the circulating ligand. Supporting Evidence: file:mouse/Epo/Epo-uniprot.txt SUBCELLULAR LOCATION: Secreted. file:mouse/Epo/Epo-uniprot.txt TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. PMID:15016652 hypoxic activation of HIF-1 alpha and its target gene EPO in mouse file:mouse/Epo/Epo-deep-research-falcon.md Falcon describes Epo as secreted into circulation from renal interstitial EPO-producing cells to act on marrow erythroid precursors. |
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Download this section (compressed HTML)Q: Which non-erythroid Epo annotations in mouse have direct endogenous-ligand evidence strong enough to keep in GO, and which should be retired as orthology-transfer over-annotations?
Suggested experts: erythropoietin signaling curators, mouse developmental biology curators
Q: Should GO annotation for Epo use erythropoietin receptor binding plus Epo-mediated signaling instead of protein kinase activator activity for ligand-driven JAK2 activation?
Suggested experts: GO molecular function curators, cytokine signaling experts
Q: Can the cardiac/coronary developmental TAS annotations from PMID:20299672 be traced to direct Epo-specific statements in full text, or should they be replaced by broader non-core angiogenesis context only?
Suggested experts: cardiovascular development curators, MGI/Reactome curators
Experiment: In primary mouse erythroid progenitors, perturb endogenous Epo or EPOR and measure JAK2, STAT5, ERK, and Bad phosphorylation together with survival and differentiation readouts.
Hypothesis: Epo core function is EPOR ligand activity that drives JAK2/STAT and survival signaling in erythroid progenitors.
Type: Endogenous ligand-receptor signaling assay
Experiment: Use Epo conditional loss or neutralization in candidate neural, immune, and cardiac contexts represented by transferred annotations, with rescue by physiological Epo, to test whether endogenous Epo is required for the annotated process.
Hypothesis: Most broad non-erythroid transferred annotations will not show a direct endogenous Epo requirement comparable to erythropoiesis.
Type: Context-specific non-erythroid validation
Experiment: Use endogenous tagging or validated antibodies in renal Epo-producing cells and erythroid target cells to distinguish intracellular production/secretory pathway signal from extracellular ligand and cell-surface receptor localization.
Hypothesis: Epo protein is secreted/extracellular, and cell-surface signal in GOA reflects EPOR-bound ligand or receptor localization rather than Epo as a membrane-resident protein.
Type: Secreted versus cell-surface localization check
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