Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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Manual orthology transfer supports receptor binding and Epo-mediated signaling from experimentally characterized erythropoietin orthologs.
"GOA ISS rows transfer erythropoietin receptor binding and erythropoietin-mediated signaling from human EPO."
Annotation inferences using phylogenetic trees
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IBA annotations correctly recover conserved Epo receptor-ligand function and erythroid signaling, but protein kinase activator activity is better represented as downstream kinase regulation.
"GOA IBA rows include EPOR binding, hormone activity, cytokine activity, erythrocyte differentiation, Epo-mediated signaling, STAT signaling, and protein kinase activator activity."
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
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Mouse-rat transfer includes plausible downstream proliferation and ERK/neural terms, but these are non-core or over-extended relative to mouse Epo erythropoiesis.
"GOA ISO rows from rat include extracellular space, proliferation, neuron projection development, T cell proliferation, cell body, neuron differentiation, and ERK cascade terms."
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
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Ensembl Compara transfer contributes many broad response and neural/immune annotations that should not be treated as core mouse Epo biology.
"GOA IEA rows include response to nutrient, salt stress, lipopolysaccharide, vitamin A, testosterone, estrogen, axon injury, electrical stimulus, hyperoxia, interleukin-1, and dexamethasone."
Electronic Gene Ontology annotations created by ARBA machine learning models
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ARBA assigns a generic response-to-stress annotation that is less informative than hypoxia-regulated Epo production and erythropoietic signaling.
"GOA includes an ARBA response to stress annotation for Epo."
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
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Mouse-human transfer captures conserved receptor binding, cytokine/hormone activity, secreted localization, erythropoiesis, Epo signaling, STAT signaling, and erythroid anti-apoptosis, but also transfers broad transcription, cell surface, osmotic, Ras, and proteasome terms requiring restraint.
"GOA ISO rows from human EPO include both canonical Epo signaling terms and many broad downstream response annotations."
Combined Automated Annotation using Multiple IEA Methods
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Combined IEA methods support receptor binding, hormone activity, extracellular localization, and proliferation as broad Epo outcomes.
"GOA IEA rows include erythropoietin receptor binding, hormone activity, extracellular region/space, and positive regulation of cell population proliferation."
UniProtKB record for mouse Epo (P07321)
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UniProt describes Epo as a hormone that binds EPOR, activates JAK2, and regulates erythrocyte proliferation/differentiation and circulating erythrocyte mass.
"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."
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UniProt localizes mouse Epo as secreted and notes kidney/liver production contexts.
"SUBCELLULAR LOCATION: Secreted. TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals."
Falcon deep research report for mouse Epo
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Falcon verifies the target as mouse erythropoietin P07321 and identifies the core function as a secreted endocrine cytokine required for definitive erythropoiesis.
"The most strongly supported functional annotation for mouse Epo (UniProt P07321) is a secreted, hypoxia-inducible endocrine cytokine produced primarily by renal cortical interstitial REP cells that binds EPOR on erythroid progenitors to activate JAK2-dependent signaling required for survival and terminal differentiation in definitive erythropoiesis."
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Falcon summarizes mouse genetic evidence that Epo/Epor loss causes severe anemia and embryonic lethality around E13-E13.5 due to impaired definitive erythropoiesis.
"Mouse Epo and EpoR loss-of-function causes defective definitive erythropoiesis, severe anemia, and embryonic lethality around E13-E13.5."
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Falcon highlights hypoxia/HIF regulation of renal Epo production and context-dependent non-erythropoietic tissue effects as secondary to the core erythropoietic function.
"A central regulatory principle is that Epo expression is strongly induced by hypoxia through the HIF system in renal EPO-producing cells."
Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia.
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Mouse renal EPO mRNA induction by hypoxia is attenuated in SOD3 knockout mice, supporting hypoxia-regulated Epo production.
"hypoxic activation of HIF-1 alpha and its target gene EPO in mouse"
BMP4 and Madh5 regulate the erythroid response to acute anemia.
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Acute anemia/hypoxia mobilizes and differentiates erythroid progenitors in mouse spleen, supporting the stress erythropoiesis context for Epo action.
"mobilization and differentiation of erythroid progenitors in the adult spleen"
Erythropoietin contributes to implantation: ectopic hemoglobin synthesis in decidual cells of mice.
SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia.
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SENP1 regulates hypoxia-induced Epo production through HIF1alpha stability; defective Epo production causes severe fetal anemia.
"embryos show severe fetal anemia stemming from deficient erythropoietin (Epo)"
Epicardial-myocardial signaling directing coronary vasculogenesis.
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The cached abstract supports a broad role for secreted growth factors in coronary development but does not itself provide direct Epo-specific evidence for the narrow cardiac GO terms.
"mediated in part by secreted growth factors"
Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin-dependent cells.
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Epo supports survival of immature erythroid cells and Epo-dependent murine cells through JNK1-dependent Bad phosphorylation.
"Epo-activated JNK1 phosphorylated Bad at threonine 201"
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The phosphorylation event is performed by JNK1, so Epo should be annotated as regulating kinase activity and erythroid survival rather than catalyzing phosphorylation.
"proliferation and survival of erythroid cells in response to Epo"
Epo binds Epor:Jak2:Lyn:Irs2
Phospho-Jak2 phosphorylates Epor
Jak2 transphosphorylates and is activated in response to Erythropoietin
p-Stat5 dissociates from Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2
Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2 phosphorylates Stat5
phospho-Epor:phospho-Jak2:Lyn:Irs2 binds Stat5
Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2:p-Crkl:Rapgef1 binds Shc1
Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2 binds Pi3k
Lyn phosphorylates Plcg1,2 in Epo receptor complex
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Reactome places secreted Epo in extracellular receptor-signaling complexes that activate EPOR/JAK2-linked pathways.
"Lyn phosphorylates Plcg1,2 in Epo receptor complex"
Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2 binds Plcg1,2
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Reactome places secreted Epo in extracellular receptor-signaling complexes that activate EPOR/JAK2-linked pathways.
"Epo:p-8Y-Epor:p-12Y-Jak2:Lyn:Irs2 binds Plcg1,2"
Epo receptor complex binds Grb2:Sos1
Jak2 phosphorylates Shc1 in Epo receptor complex
Epo receptor complex mediates exchange of GDP for GTP bound to Ras
Jak2 phosphorylates Vav1 in Epo receptor complex
Epo receptor complex binds Crkl:Rapgef1
Lyn phosphorylates Crkl in Epo receptor complex
Epor-associated Plcg hydrolyzes phosphatidylinositol bisphosphate