Fer2LCH encodes the light-chain homolog (L subunit) of Drosophila secreted ferritin and is the predominant ferritin subunit at all life stages. Twelve Fer2LCH and twelve Fer1HCH subunits assemble in the secretory pathway into a 24-mer iron-storage cage that is loaded with iron in the Golgi and secreted into hemolymph; the L subunits supply nucleation sites for the ferrihydrite iron core, whereas the H subunits provide the ferroxidase center. Ferritin is required in midgut enterocytes for dietary iron absorption, exporting iron toward the hemolymph, and in other tissues for sequestering and detoxifying excess iron, and Fer2LCH mutants die during embryogenesis. In an RNAi screen in clock neurons, Fer2LCH silencing disrupted circadian locomotor rhythms in constant darkness and the oscillation of PER and TIM, linking iron storage to clock function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | EXP PMID:26192321 Ferritin Is Required in Multiple Tissues during Drosophila m... | ACCEPT | Summary: Fluorescently tagged Fer2LCH is secreted via the secretory pathway. Reason: Experimental support for secretion of fly ferritin. Supporting Evidence: PMID:26192321 Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. PMID:17603097 In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. |
| GO:0005576 extracellular region | HDA PMID:15466469 Proteomic analysis of the Drosophila larval hemolymph clot. | ACCEPT | Summary: Ferritin identified in cell-free larval hemolymph proteome. Reason: High-throughput detection consistent with the well-established secretion of fly ferritin. Supporting Evidence: PMID:15466469 our two-dimensional protein map of cell-free Drosophila hemolymph includes many additional proteins PMID:17603097 In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location "Secreted" mapping. Reason: Supported by experimental evidence for secretion into hemolymph. Supporting Evidence: PMID:17603097 In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. |
| GO:0005794 Golgi apparatus | IDA PMID:17603097 Homeostatic mechanisms for iron storage revealed by genetic ... | ACCEPT | Summary: GFP-tagged ferritin localizes to the Golgi in midgut iron-region cells. Reason: Direct live-imaging and colocalization with the Golgi marker Lava lamp; iron loading of insect ferritin occurs in the secretory pathway. Supporting Evidence: PMID:17603097 Confocal images from a single cell in the iron region clearly showed that all GFP-ferritin localized within the Golgi compartment PMID:17603097 In vivo expression of GFP-tagged holoferritin confirmed that iron-loaded ferritin molecules traffic through the Golgi organelle and are secreted into hemolymph. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location "Golgi apparatus" mapping. Reason: Supported by the IDA data from the same study used by UniProt. Supporting Evidence: PMID:17603097 Confocal images from a single cell in the iron region clearly showed that all GFP-ferritin localized within the Golgi compartment |
| GO:0006826 iron ion transport | IEA GO_REF:0000002 | ACCEPT | Summary: Iron ion transport from the ferritin InterPro signature. Reason: Unlike vertebrate ferritin, secreted insect ferritin moves iron between cells (out of enterocytes into hemolymph), so iron transport is a genuine role here. Supporting Evidence: PMID:26192321 Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. PMID:23064556 These results suggest an essential role of ferritin in removing iron from enterocytes across the basolateral membrane. |
| GO:0006879 intracellular iron ion homeostasis | IDA PMID:10077577 Iron availability dramatically alters the distribution of fe... | ACCEPT | Summary: Iron-dependent regulation of ferritin subunit messages; ferritin buffers cellular iron. Reason: Ferritin is the main iron-storage protein; the experimental annotation is consistent with the established role in iron homeostasis, and the curator read the full paper. Supporting Evidence: PMID:10077577 Iron significantly increases the amount of ferritin HCH messages PMID:23064556 Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification |
| GO:0006879 intracellular iron ion homeostasis | IEA GO_REF:0000002 | ACCEPT | Summary: Iron homeostasis from the ferritin InterPro signature. Reason: Core role of ferritin. Supporting Evidence: PMID:23064556 Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification |
| GO:0008198 ferrous iron binding | IDA PMID:10077577 Iron availability dramatically alters the distribution of fe... | KEEP AS NON CORE | Summary: Ferrous iron binding annotated to the L subunit. Reason: Iron binding by the assembled holoferritin is well established, but the L chain mainly nucleates the ferric core and lacks the ferroxidase center that binds Fe(2+); keep as a complex-level, non-core property and defer to the curator who read the full text. Supporting Evidence: PMID:17603097 The H subunit contains a ferroxidase center, which enables the mature heteropolymer to oxidize soluble ferrous iron, whereas the L chain provides the nucleation centers for deposition of the ferrihydrite mineral |
| GO:0008199 ferric iron binding | IEA GO_REF:0000002 | ACCEPT | Summary: Ferric iron binding from the ferritin InterPro signatures. Reason: Ferritin stores iron as a ferric oxyhydroxide core within the 24-mer cage. Supporting Evidence: PMID:17603097 The H subunit contains a ferroxidase center, which enables the mature heteropolymer to oxidize soluble ferrous iron, whereas the L chain provides the nucleation centers for deposition of the ferrihydrite mineral |
| GO:0009620 response to fungus | HEP PMID:15556270 Peptidomic and proteomic analyses of the systemic immune res... | KEEP AS NON CORE | Summary: Ferritin abundance in hemolymph changes after microbial (including fungal) challenge. Reason: Expression-pattern evidence; iron withholding by ferritin is a plausible part of nutritional immunity, but the annotation reflects induction rather than a defined immune activity. Supporting Evidence: PMID:15556270 differential analyses of blood content (hemolymph) from immune-challenged versus control Drosophila were performed |
| GO:0012505 endomembrane system | HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi... | ACCEPT | Summary: LOPIT organelle proteomics places Fer2LCH in the endomembrane fraction. Reason: Consistent with assembly and iron loading of fly ferritin in the secretory pathway. Supporting Evidence: PMID:19317464 We determine the subcellular distribution of hundreds of proteins, and protein complexes. PMID:17603097 Confocal images from a single cell in the iron region clearly showed that all GFP-ferritin localized within the Golgi compartment |
| GO:0070288 ferritin complex | IDA PMID:10077577 Iron availability dramatically alters the distribution of fe... | ACCEPT | Summary: Fer1HCH and Fer2LCH assemble into the 24-subunit ferritin cage in 1:1 stoichiometry. Reason: The ferritin heteropolymer is the functional unit; subunit membership of the complex is core. Supporting Evidence: PMID:26192321 inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry PMID:17603097 The H subunit contains a ferroxidase center, which enables the mature heteropolymer to oxidize soluble ferrous iron, whereas the L chain provides the nucleation centers for deposition of the ferrihydrite mineral |
| GO:0098711 iron ion import across plasma membrane | IMP PMID:23064556 Ferritin is the key to dietary iron absorption and tissue ir... | MODIFY | Summary: Midgut ferritin knockdown traps iron in enterocytes and causes systemic iron deficiency. Reason: The data show ferritin is required for dietary iron absorption by carrying iron out of enterocytes across the basolateral side; this is efflux into hemolymph, not import across the plasma membrane into a cell, and ferritin is not a membrane transporter. Intestinal iron absorption captures the experimental finding. Proposed replacements: intestinal iron absorption Supporting Evidence: PMID:23064556 These results suggest an essential role of ferritin in removing iron from enterocytes across the basolateral membrane. PMID:23064556 Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification |
| GO:1990461 detoxification of iron ion | IMP PMID:23064556 Ferritin is the key to dietary iron absorption and tissue ir... | ACCEPT | Summary: Tissue-specific ferritin knockdown causes local iron accumulation and tissue damage. Reason: Direct genetic evidence that ferritin sequesters and exports excess iron to protect tissues. Supporting Evidence: PMID:23064556 tissue-specific ferritin knockdown also caused local iron accumulation (100% increase) and resulted in severe tissue damage PMID:23064556 Drosophila ferritin is essential to two key aspects of iron homeostasis: dietary iron absorption and tissue iron detoxification |
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Download this section (compressed HTML)Q: Why does fly secreted ferritin maintain a strict 1:1 H:L ratio when Fer2LCH mRNA lacks an IRE, and what post-transcriptional mechanism enforces it?
Experiment: Rescue Fer2LCH mutants with transgenes mutating the predicted interior acidic nucleation residues and measure holoferritin iron content, secretion and viability.
Hypothesis: Fer2LCH nucleation residues are required for iron loading but not for cage assembly or secretion.
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Download this section (compressed HTML)Ferritin 2 light chain homologue (Fer2LCH) encodes one of two subunits of the major iron storage complex, the ferritin molecule. In insects, ferritin is assembled from 12 Fer1HCH and 12 Fer2LCH subunits and can be found in the secretory pathway of cells and in hemolymph. The product of Fer2LCH provides iron nucleation sites in the internal cavity of the complex required for iron mineralization and is essential for embryogenesis.
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