spi encodes Spitz, a Drosophila EGF-family ligand synthesized as a membrane-tethered precursor in the secretory pathway. After Star-dependent trafficking and Rhomboid-dependent intramembrane proteolysis, processed Spitz is released to bind and activate the EGF receptor in neighboring cells. Spitz drives EGFR/Ras/MAPK signaling during embryonic ectoderm patterning, photoreceptor recruitment, glial migration, muscle development, and other local inductive events.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping places the type I Spitz precursor on the Golgi membrane. Reason: Golgi membrane is a correct core location: Star exports Spitz from the ER to the Golgi and Rhomboid-1 cleaves Spitz in the Golgi. Supporting Evidence: file:DROME/spi/spi-uniprot.txt DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. PMID:11672524 Golgi apparatus. Rhomboid-1 is localized in the Golgi, where it promotes the cleavage of Spitz. |
| GO:0001713 ectodermal cell fate determination | IMP PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | KEEP AS NON CORE | Summary: Secreted Spitz is required in a ventral-ectoderm EGFR patterning context. Reason: This is a genuine developmental output of the Spi-EGFR ligand pathway, but ectodermal fate determination is a context-specific embryonic role rather than the core molecular function of Spitz. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0003015 heart process | IMP PMID:20523889 Affecting Rhomboid-3 function causes a dilated heart in adul... | KEEP AS NON CORE | Summary: Rhomboid-3-dependent activation of the Spitz-EGFR pathway is required for adult heart function. Reason: The adult cardiac phenotype is a real physiological output of the Rho/Spi/EGFR pathway, but it is a tissue-specific role downstream of the secreted ligand activity. Supporting Evidence: PMID:20523889 rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:10688656 The interaction between the Drosophila secreted protein argo... | ACCEPT | Summary: Biochemical and cell-based data support binding of secreted Spitz to the Drosophila EGFR extracellular domain. Reason: The term directly captures Spitz as an EGFR-family ligand that binds the DER/EGFR extracellular domain. Supporting Evidence: PMID:10688656 Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER. |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:20957186 Polarized secretion of Drosophila EGFR ligand from photorece... | ACCEPT | Summary: Biochemical and cell-based data support binding of secreted Spitz to the Drosophila EGFR extracellular domain. Reason: The term directly captures Spitz as an EGFR-family ligand that binds the DER/EGFR extracellular domain. Supporting Evidence: PMID:10688656 Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER. |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: Biochemical and cell-based data support binding of secreted Spitz to the Drosophila EGFR extracellular domain. Reason: The term directly captures Spitz as an EGFR-family ligand that binds the DER/EGFR extracellular domain. Supporting Evidence: PMID:10688656 Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER. |
| GO:0005154 epidermal growth factor receptor binding | IDA PMID:9531530 EGF domain swap converts a drosophila EGF receptor activator... | ACCEPT | Summary: Biochemical and cell-based data support binding of secreted Spitz to the Drosophila EGFR extracellular domain. Reason: The term directly captures Spitz as an EGFR-family ligand that binds the DER/EGFR extracellular domain. Supporting Evidence: PMID:10688656 Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER. |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000002 | ACCEPT | Summary: The Gurken/Spitz InterPro mapping correctly infers EGFR binding for the Drosophila Spitz-family ligand. Reason: The electronic mapping is consistent with direct Drosophila biochemical and signaling evidence for Spi as a DER/EGFR ligand. Supporting Evidence: file:DROME/spi/spi-uniprot.txt DR InterPro; IPR043403; Gurken/Spitz. PMID:10688656 secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER |
| GO:0005515 protein binding | IPI PMID:15329724 Argos inhibits epidermal growth factor receptor signalling b... | REMOVE | Summary: The Argos-Spitz interaction is real, but generic protein binding is not an informative Spi molecular function. Reason: This IPI row reflects Argos sequestration of the Spitz ligand. That interaction modulates signaling extracellularly, but GO:0005515 says only that two proteins bind and loses the specific biology; there is no more specific Argos-binding MF term to substitute here. Supporting Evidence: PMID:15329724 Argos binds tightly to the EGF motif of Spitz and forms a 1:1 (Spitz:Argos) complex |
| GO:0005515 protein binding | IPI PMID:18500331 Structural basis for EGFR ligand sequestration by Argos. | REMOVE | Summary: The crystal structure establishes an Argos-Spitz complex, but generic protein binding is not an informative Spi molecular function. Reason: The paper defines how Argos clamps Spitz to sequester an EGFR ligand. That is a real protein-protein interaction, but the bare GO:0005515 annotation is too generic and should not be retained as a functional assertion for Spi. Supporting Evidence: PMID:18500331 Argos bound to an EGFR ligand |
| GO:0005515 protein binding | IPI PMID:20723758 Structural basis for negative cooperativity in growth factor... | MODIFY | Summary: The structural EGFR paper supports Spi-EGFR binding rather than unqualified protein binding. Reason: The supporting entity is Egfr and the publication solved Spitz-bound Drosophila EGFR extracellular structures, so the row should be annotated to the specific receptor-binding term. Proposed replacements: epidermal growth factor receptor binding Supporting Evidence: PMID:20723758 We describe crystal structures of s-dEGFR bound to its growth factor ligand Spitz |
| GO:0005576 extracellular region | IDA PMID:11672524 Regulated intracellular ligand transport and proteolysis con... | ACCEPT | Summary: Cleavage of the transmembrane Spitz precursor releases the active extracellular ligand. Reason: The active EGFR ligand is released from its membrane precursor and acts extracellularly, matching the GO-CAM location for the spi ligand activity. Supporting Evidence: PMID:11672524 This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml term: GO:0005576 |
| GO:0005576 extracellular region | IDA PMID:17304216 Rhomboid cleaves Star to regulate the levels of secreted Spi... | ACCEPT | Summary: Cleavage of the transmembrane Spitz precursor releases the active extracellular ligand. Reason: The active EGFR ligand is released from its membrane precursor and acts extracellularly, matching the GO-CAM location for the spi ligand activity. Supporting Evidence: PMID:11672524 This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml term: GO:0005576 |
| GO:0005576 extracellular region | IDA PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: Cleavage of the transmembrane Spitz precursor releases the active extracellular ligand. Reason: The active EGFR ligand is released from its membrane precursor and acts extracellularly, matching the GO-CAM location for the spi ligand activity. Supporting Evidence: PMID:11672524 This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml term: GO:0005576 |
| GO:0005576 extracellular region | IDA PMID:7651519 Inhibition of Drosophila EGF receptor activation by the secr... | ACCEPT | Summary: Cleavage of the transmembrane Spitz precursor releases the active extracellular ligand. Reason: The active EGFR ligand is released from its membrane precursor and acts extracellularly, matching the GO-CAM location for the spi ligand activity. Supporting Evidence: PMID:11672524 This defines a novel growth factor release mechanism that is distinct from metalloprotease-dependent shedding from the cell surface. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml term: GO:0005576 |
| GO:0005783 endoplasmic reticulum | IDA PMID:15469842 Small wing PLCgamma is required for ER retention of cleaved ... | ACCEPT | Summary: Cleaved Spitz can accumulate in the endoplasmic reticulum. Reason: This is a correct trafficking location for Spitz in the secretory pathway and for ER-retained cleaved Spitz in the cited eye-development study. Supporting Evidence: PMID:15469842 when a cleaved variant of Spitz (cSpi) was expressed, it accumulated in the ER, both in embryos and in cell culture. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping places the membrane-tethered Spitz precursor on the ER membrane. Reason: ER membrane is correct for the transmembrane pro-protein before Star/Rhomboid-dependent trafficking and cleavage. UniProt's curated subcellular location (experimental, from PMID:11672524) places the single-pass type I precursor in the ER membrane. Supporting Evidence: file:DROME/spi/spi-uniprot.txt Endoplasmic reticulum membrane {ECO:0000269|PubMed:11672524} file:DROME/spi/spi-uniprot.txt Single-pass type I membrane protein {ECO:0000269|PubMed:11672524} |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping places Spitz on the plasma membrane. Reason: The membrane-tethered pro-protein can reach the cell surface, so plasma membrane is an appropriate location for the precursor and its membrane-tethered forms. Supporting Evidence: file:DROME/spi/spi-uniprot.txt DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. PMID:23902690 We found that the pro-protein can reach the cell surface in the |
| GO:0007166 cell surface receptor signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: The PAINT row captures the inherited EGF-ligand role at an overly broad signaling-pathway level. Reason: Spitz is not merely a generic cell-surface-receptor ligand; in Drosophila it is a ligand in the EGFR pathway, which is already the production GO-CAM biological-process context for spi. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000960795 SUPPORTS TRANSFER PAINT supports an inherited EGF-ligand signaling role for spi; the issue is only that GO:0007166 is a true but uninformative parent of the Drosophila EGFR pathway term. Proposed replacements: epidermal growth factor receptor signaling pathway Supporting Evidence: file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:10349622 An interplay between two EGF-receptor ligands, Vein and Spit... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:10652272 Rhomboid and Star facilitate presentation and processing of ... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:10688656 The interaction between the Drosophila secreted protein argo... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:10918615 Evidence that Argos is an antagonistic ligand of the EGF rec... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:14555990 DroVav, the Drosophila melanogaster homologue of the mammali... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:7651519 Inhibition of Drosophila EGF receptor activation by the secr... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:8565833 Argos transcription is induced by the Drosophila EGF recepto... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:9531530 EGF domain swap converts a drosophila EGF receptor activator... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:11023685 brother of rhomboid, a rhomboid-related gene expressed durin... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:11141565 Guidance of cell migration by EGF receptor signaling during ... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:17512517 The EGFR ligands Spitz and Keren act cooperatively in the Dr... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:16459296 Palmitoylation of the EGFR ligand Spitz by Rasp increases Sp... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:20957186 Polarized secretion of Drosophila EGFR ligand from photorece... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:23902690 Trafficking of the EGFR ligand Spitz regulates its signaling... | ACCEPT | Summary: Spitz is the activating Drosophila EGFR ligand and the annotation to the EGFR pathway captures its core signaling role. Reason: Cleaved, secreted Spitz activates the Drosophila EGF receptor/DER pathway; this is the central activity of the gene product. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. |
| GO:0007298 border follicle cell migration | IMP PMID:11141565 Guidance of cell migration by EGF receptor signaling during ... | KEEP AS NON CORE | Summary: EGFR signaling guides border-cell migration during oogenesis, and later work directly identified Spitz as one of the oocyte ligands. Reason: Border follicle-cell migration is a true but specialized oogenesis context for Spi-EGFR signaling, not the conserved core activity. Supporting Evidence: PMID:16712835 Two ligands, Keren and Spitz, guided border cells |
| GO:0007391 dorsal closure | IMP PMID:28628612 Novel interplay between JNK and Egfr signaling in Drosophila... | KEEP AS NON CORE | Summary: spi mutants impair EGFR/ERK signaling in the lateral epidermis during dorsal closure. Reason: Dorsal closure is a morphogenetic output of local Spi-EGFR pathway activation, so it should be kept as a non-core developmental role. Supporting Evidence: PMID:28628612 dpErk staining is evident in the lateral epidermis |
| GO:0007421 stomatogastric nervous system development | IMP PMID:11269504 Tip cell-derived RTK signaling initiates cell movements in t... | KEEP AS NON CORE | Summary: Tip cells secrete Spitz to trigger local RTK signaling in stomatogastric nervous system morphogenesis. Reason: The annotation is supported, but stomatogastric nervous system development is a specific developmental deployment of the Spi ligand. Supporting Evidence: PMID:11269504 tip cells secrete the DER ligand Spitz and trigger local RTK signaling |
| GO:0007422 peripheral nervous system development | IMP PMID:12967983 Reciprocal interactions between neurons and glia are require... | KEEP AS NON CORE | Summary: Spitz-EGFR signaling contributes to peripheral glial development. Reason: Peripheral nervous system development is a real developmental output, but not Spi's core molecular role. Supporting Evidence: PMID:12967983 the EGFR ligands Spitz and Vein play roles in peripheral glial development |
| GO:0007438 oenocyte development | IGI PMID:12050142 abdominal A specifies one cell type in Drosophila by regulat... | KEEP AS NON CORE | Summary: Abdominal-A promotes oenocyte development through rhomboid-dependent processing of secreted Spitz. Reason: Oenocyte development is a specific Hox-regulated target-tissue outcome of Spitz release, so it should be retained as non-core. Supporting Evidence: PMID:12050142 Rhomboid (Rho), a processing factor for the EGF receptor ligand, secreted Spitz |
| GO:0007438 oenocyte development | IMP PMID:12050142 abdominal A specifies one cell type in Drosophila by regulat... | KEEP AS NON CORE | Summary: Abdominal-A promotes oenocyte development through rhomboid-dependent processing of secreted Spitz. Reason: Oenocyte development is a specific Hox-regulated target-tissue outcome of Spitz release, so it should be retained as non-core. Supporting Evidence: PMID:12050142 Rhomboid (Rho), a processing factor for the EGF receptor ligand, secreted Spitz |
| GO:0007476 imaginal disc-derived wing morphogenesis | IMP PMID:16648592 Epidermal growth factor receptor and transforming growth fac... | KEEP AS NON CORE | Summary: Loss of one spi copy measurably changes Drosophila wing shape. Reason: The wing-shape phenotype is consistent with a non-core wing morphogenesis role downstream of the EGFR ligand. Supporting Evidence: PMID:16648592 a mutation in spi caused a shape change relative to its congenics |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:19141677 EGFR signaling regulates the proliferation of Drosophila adu... | KEEP AS NON CORE | Summary: Spitz and Keren are AMP-expressed EGFR ligands that can provide autocrine mitogenic stimulus to adult midgut progenitors. Reason: Adult midgut progenitor proliferation is a tissue-specific mitogenic output of EGFR signaling, while Spi itself remains an EGFR ligand. Supporting Evidence: PMID:19141677 Two stronger EGFR ligands, Spitz and Keren, are expressed by the AMPs themselves and provide an additional, autocrine mitogenic stimulus to the AMPs during late larval stages. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:21176204 Drosophila EGFR pathway coordinates stem cell proliferation ... | KEEP AS NON CORE | Summary: The Spitz/Keren/Vein EGFR ligand set is induced in infection-stimulated adult gut remodeling and stem-cell proliferation. Reason: This is a non-core stress and tissue-repair role for Spi-EGFR signaling rather than a separate molecular function. Supporting Evidence: PMID:21176204 The EGFR pathway is activated by the EGF ligands, Spitz, Keren and Vein |
| GO:0008355 olfactory learning | IMP PMID:23512935 EGFR signaling in the brain is necessary for olfactory learn... | KEEP AS NON CORE | Summary: The abstract reports that altering EGFR ligand signaling, including Spitz, changes larval olfactory learning performance. Reason: Olfactory learning is a specialized neural consequence of maintaining appropriate EGFR signaling levels in mushroom bodies, so this is not a core Spi function. Supporting Evidence: PMID:23512935 targeted expression of a constitutively active form of the ligand Spitz also led to a significantly reduced learning ability |
| GO:0010629 negative regulation of gene expression | IMP PMID:28628612 Novel interplay between JNK and Egfr signaling in Drosophila... | MARK AS OVER ANNOTATED | Summary: EGFR signaling represses scarface expression during dorsal closure, downstream of spi and rhomboid pathway activation. Reason: The scaf repression is a downstream transcriptional effect of Egfr signaling in lateral epidermal cells. spi participates as the upstream ligand, but the broad gene-expression term overstates its direct role and duplicates the dorsal-closure and EGFR-signaling context. Supporting Evidence: PMID:28628612 Egfr signaling inhibits scaf expression in lateral epidermis cells |
| GO:0016020 membrane | IDA PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: Spitz is a membrane protein before proteolytic release of its extracellular signaling domain. Reason: The general membrane annotation is less specific than the ER, Golgi, and plasma-membrane rows, but it is correct for the type I Spitz precursor. Supporting Evidence: file:DROME/spi/spi-uniprot.txt FT TRANSMEM 144..164 |
| GO:0016318 ommatidial rotation | IMP PMID:14507782 Egfr signaling regulates ommatidial rotation and cell motili... | KEEP AS NON CORE | Summary: EGFR signaling participates in ommatidial rotation downstream of the Spitz-EGFR receptor-ligand module. Reason: Ommatidial rotation is a specific eye morphogenesis output and not the core Spi ligand activity. Supporting Evidence: PMID:14507782 Egfr signaling regulates ommatidial rotation and cell motility in the Drosophila eye |
| GO:0035225 determination of genital disc primordium | IMP PMID:15893978 Allocation and specification of the genital disc precursor c... | KEEP AS NON CORE | Summary: The genital disc precursor study implicates EGF receptor and spitz-group genes in allocating those cells. Reason: Genital disc primordium determination is a specialized embryonic fate decision downstream of Spi-EGFR signaling. Supporting Evidence: PMID:15893978 the GDPCs. The allocation of the GDPCs from the ventral epidermis requires the function of ventral patterning genes, including the EGF receptor and the spitz |
| GO:0035277 spiracle morphogenesis, open tracheal system | IMP PMID:15930099 Hox-controlled reorganisation of intrasegmental patterning c... | UNDECIDED | Summary: The posterior spiracle paper implicates the EGFR/rhomboid patterning module in spiracle morphogenesis. Reason: The abstract supports an EGFR/rhomboid role, and a FlyBase full-text curator may have seen a spi perturbation supporting the IMP row, but the cached abstract does not expose a direct spi experiment. Supporting Evidence: PMID:15930099 Epidermal Growth Factor Receptor (Egfr) pathways provide specific inputs for posterior spiracle morphogenesis |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:17055987 Control of compartment size by an EGF ligand from neighborin... | KEEP AS NON CORE | Summary: Spitz supplied from neighboring cells supports survival and growth of the posterior embryonic compartment. Reason: Negative regulation of apoptosis is a context-specific outcome of Spi/EGFR availability during compartment-size control. Supporting Evidence: PMID:17055987 Spi/EGFR activity stimulates P compartment cell enlargement and survival |
| GO:0043703 photoreceptor cell fate determination | IGI PMID:7833286 The spitz gene is required for photoreceptor determination i... | KEEP AS NON CORE | Summary: Genetic data support a Spitz-EGFR requirement in photoreceptor fate determination. Reason: Photoreceptor determination is a canonical but context-specific eye-development deployment of Spi-EGFR signaling. Supporting Evidence: PMID:7833286 spitz gene is required for photoreceptor determination |
| GO:0046530 photoreceptor cell differentiation | IMP PMID:11245584 Role of the EGFR/Ras/Raf pathway in specification of photore... | KEEP AS NON CORE | Summary: EGFR/Ras/Raf signaling is required for photoreceptor recruitment and differentiation in the Drosophila retina. Reason: This eye differentiation role is downstream of Spi-mediated EGFR activation and should be kept as non-core. Supporting Evidence: PMID:11245584 The Egfr, ras and raf genes are each found to be essential for recruitment of R1-R7 cells PMID:7833286 spitz gene is required for photoreceptor determination |
| GO:0048018 receptor ligand activity | IDA PMID:10688656 The interaction between the Drosophila secreted protein argo... | ACCEPT | Summary: Spitz acts as a receptor ligand that activates Drosophila EGFR/DER. Reason: The EGF-like domain of cleaved Spitz is an extracellular receptor-activating ligand, and this receptor-ligand activity is the molecular function modeled for spi in the production Drosophila GO-CAM. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0048018 receptor ligand activity | IDA PMID:15329724 Argos inhibits epidermal growth factor receptor signalling b... | ACCEPT | Summary: Spitz acts as a receptor ligand that activates Drosophila EGFR/DER. Reason: The EGF-like domain of cleaved Spitz is an extracellular receptor-activating ligand, and this receptor-ligand activity is the molecular function modeled for spi in the production Drosophila GO-CAM. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0048018 receptor ligand activity | IDA PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: Spitz acts as a receptor ligand that activates Drosophila EGFR/DER. Reason: The EGF-like domain of cleaved Spitz is an extracellular receptor-activating ligand, and this receptor-ligand activity is the molecular function modeled for spi in the production Drosophila GO-CAM. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0048018 receptor ligand activity | IDA PMID:7651519 Inhibition of Drosophila EGF receptor activation by the secr... | ACCEPT | Summary: Spitz acts as a receptor ligand that activates Drosophila EGFR/DER. Reason: The EGF-like domain of cleaved Spitz is an extracellular receptor-activating ligand, and this receptor-ligand activity is the molecular function modeled for spi in the production Drosophila GO-CAM. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0048018 receptor ligand activity | IDA PMID:9531530 EGF domain swap converts a drosophila EGF receptor activator... | ACCEPT | Summary: Spitz acts as a receptor ligand that activates Drosophila EGFR/DER. Reason: The EGF-like domain of cleaved Spitz is an extracellular receptor-activating ligand, and this receptor-ligand activity is the molecular function modeled for spi in the production Drosophila GO-CAM. Supporting Evidence: PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml title: epidermal growth factor receptor signaling pathway via spi-Egfr (D.mel) |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000002 | ACCEPT | Summary: The Gurken/Spitz InterPro mapping correctly infers receptor ligand activity for Spitz-family EGFR ligands. Reason: This electronic annotation matches the experimentally established Spi receptor-ligand activity and the Drosophila GO-CAM model for spi-Egfr signaling. Supporting Evidence: file:DROME/spi/spi-uniprot.txt DR InterPro; IPR043403; Gurken/Spitz. file:gocams/60ad85f700001873/60ad85f700001873-src.yaml term: GO:0048018 |
| GO:0048149 behavioral response to ethanol | IMP PMID:19464045 Happyhour, a Ste20 family kinase, implicates EGFR signaling ... | UNDECIDED | Summary: The ethanol-response row is likely an EGFR-pathway phenotype, but the cached abstract does not expose a direct spi perturbation. Reason: The publication abstract supports EGFR signaling in ethanol sensitivity; full-text evidence would be needed to decide whether spi itself was assayed or this was propagated from other EGFR-pathway components. Supporting Evidence: PMID:19464045 the epidermal growth factor (EGF)-signaling pathway regulates ethanol sensitivity in Drosophila |
| GO:0048865 stem cell fate commitment | IMP PMID:20463031 Drosophila adult muscle precursors form a network of interco... | KEEP AS NON CORE | Summary: A rhomboid-triggered EGF pathway controls specification and maintenance of adult muscle precursors. Reason: The stem-like adult-muscle-precursor phenotype is a developmental output of the Spi-processing pathway, not the core molecular function. Supporting Evidence: PMID:20463031 rhomboid-triggered EGF signalling pathway controls both the specification and the subsequent maintenance of AMP cells |
| GO:0050769 positive regulation of neurogenesis | IMP PMID:24139822 Conserved miR-8/miR-200 defines a glial niche that controls ... | KEEP AS NON CORE | Summary: Glial Spitz activates EGFR in the optic-lobe neuroepithelium to promote neuroepithelial proliferation and neuroblast formation. Reason: The term captures a real neural-development output, but it is context-specific relative to the core secreted EGFR-ligand activity. Supporting Evidence: PMID:24139822 Spitz, a transforming growth factor Ξ± (TGF-Ξ±)-like ligand that triggers epidermal growth factor receptor (EGFR) activation to promote neuroepithelial proliferation and neuroblast formation |
| GO:0061331 epithelial cell proliferation involved in Malpighian tubule morphogenesis | IMP PMID:9637680 Seven-up, the Drosophila homolog of the COUP-TF orphan recep... | KEEP AS NON CORE | Summary: Tip-cell EGFR signaling drives proliferation during Malpighian tubule morphogenesis through the same Rho/Spi ligand-release cassette. Reason: The Malpighian-tubule phenotype is a specific proliferative output of the Spitz-EGFR pathway and should be kept as non-core. Supporting Evidence: PMID:9637680 same key components of the EGFR cascade are required |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IDA PMID:9531530 EGF domain swap converts a drosophila EGF receptor activator... | ACCEPT | Summary: Secreted Spitz activates DER/EGFR-dependent ERK/MAPK signaling. Reason: Positive regulation of the ERK cascade is a direct downstream consequence of Spi binding and activating DER/EGFR. Supporting Evidence: PMID:9531530 Spitz (Spi), which is a potent activator; Vein (Vn), which is a moderate activator; and Argos (Aos), which is an inhibitor. |
| GO:1903688 positive regulation of border follicle cell migration | IMP PMID:16712835 Multiple EGFR ligands participate in guiding migrating borde... | KEEP AS NON CORE | Summary: Spitz is one of the EGFR ligands that can guide migrating border cells toward the oocyte. Reason: This is a direct but oogenesis-specific migration role for the Spi ligand. Supporting Evidence: PMID:16712835 Two ligands, Keren and Spitz, guided border cells |
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Download this section (compressed HTML)spitz (spi) encodes the cardinal Egfr ligand that is produced as a transmembrane precursor and processed by the products of S and rho. Its roles include growth regulation, cell survival and developmental patterning.
Provider deep research was unavailable in this environment: Falcon required
agentapi on PATH, and the Perplexity/OpenAI fallbacks had no API keys
configured. This annotation-review pass therefore relied on the seeded GOA
review, UniProt Q01083, cached PMID records under publications/, and the
cached Drosophila spi-Egfr GO-CAM where it was useful.
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