drk encodes the Drosophila GRB2-family adaptor Downstream of receptor kinase. Its SH2 domain binds phosphotyrosine motifs on activated receptor tyrosine kinases and its SH3 domains bind proline-rich partners such as Sos and Dos, recruiting Ras activators and scaffolds to receptor complexes. Drk couples EGFR, Sevenless, Torso, and additional RTKs to Ras/MAPK signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001784 phosphotyrosine residue binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: phosphotyrosine residue binding, the conserved SH2-domain activity of Drk/GRB2 adaptors. Reason: Drk is an SH2/SH3 receptor-proximal adaptor whose SH2 domain recognizes phosphotyrosine motifs on activated RTKs and phosphorylated scaffolds; this IBA is placed on the same GRB2/Sem-5/DRK family node as the direct fly and vertebrate evidence. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0001784 phosphotyrosine residue binding | IPI PMID:9885560 Opposing actions of CSW and RasGAP modulate the strength of ... | ACCEPT | Summary: IPI: phosphotyrosine-dependent Drk recruitment in the Torso pathway. Reason: Corkscrew acts as a phosphorylated adaptor for Drk in Torso signaling, so the row captures Drk SH2/phosphotyrosine recognition in a direct Drosophila RTK context. Supporting Evidence: PMID:9885560 CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation. |
| GO:0005118 sevenless binding | IDA PMID:20980384 Competition between SOCS36E and Drk modulates Sevenless rece... | ACCEPT | Summary: IDA: Drk binding to the activated Sevenless receptor. Reason: Sevenless binding is one of the canonical Drk SH2-domain interactions that couples Sev to Ras/MAPK during R7 photoreceptor specification. Supporting Evidence: PMID:20980384 demonstrate that Sev binds directly to either the suppressor protein SOCS36E or the adaptor protein Drk. |
| GO:0005118 sevenless binding | IPI PMID:7781603 Biochemical and genetic analysis of the Drk SH2/SH3 adaptor ... | ACCEPT | Summary: IPI: Drk interaction with Sevenless in the eye RTK pathway. Reason: The cited biochemical/genetic work showed that the Sev cytoplasmic tail provides a Drk SH2 recognition site, directly supporting Sevenless binding by Drk. Supporting Evidence: PMID:7781603 Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. |
| GO:0005118 sevenless binding | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Drk binding to activated Sevenless. Reason: Drk SH2-domain binding to receptor tyrosine kinases, including Sevenless, is a core molecular function of this adaptor and is coupled to Sos recruitment through its SH3 domains. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0005154 epidermal growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: epidermal growth factor receptor binding by the GRB2/Sem-5/DRK family. Reason: The IBA is sound: fly Drk is recruited to activated DER/EGFR, and EGFR binding is conserved among Drk/GRB2-family receptor-proximal adaptors. Supporting Evidence: PMID:7601354 Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA/ARBA: epidermal growth factor receptor binding. Reason: The electronic assertion is consistent with direct Drosophila evidence that Drk associates with autophosphorylated DER/EGFR and with the conserved GRB2-family role in EGFR signaling. Supporting Evidence: PMID:7601354 Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. |
| GO:0005154 epidermal growth factor receptor binding | IPI PMID:21340027 D-Cbl binding to Drk leads to dose-dependent down-regulation... | ACCEPT | Summary: IPI: Drk binding to Drosophila EGFR. Reason: D-CblL-dependent EGFR down-regulation uses Drk, and the paper specifically used a Drk SH2 mutant that loses EGFR binding; the EGFR-binding annotation is therefore informative and correct. Supporting Evidence: PMID:21340027 Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. |
| GO:0005515 protein binding | IPI PMID:12128212 SH3 domain-mediated binding of the Drk protein to Dos is an ... | MODIFY | Summary: IPI: Drk-Dos binding captured as generic protein binding. Reason: The paper maps Dos recruitment to the Drk C-terminal SH3 domain and Dos proline-rich motifs; the mechanistic molecular function is proline-rich region binding, not bare protein binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:12128212 Drk binds with its SH2 domain to the autophosphorylated Sev receptor while the C-terminal SH3 domain is able to associate with Dos. |
| GO:0005515 protein binding | IPI PMID:21340027 D-Cbl binding to Drk leads to dose-dependent down-regulation... | MODIFY | Summary: IPI: Drk-D-CblL binding captured as generic protein binding. Reason: D-CblL binds Drk through a proline-rich motif and functions with Drk in EGFR down-regulation; GO:0070064 records the SH3/proline-rich recognition that the generic binding row hides. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:21340027 Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. |
| GO:0005515 protein binding | IPI PMID:22615583 Drosophila activated Cdc42 kinase has an anti-apoptotic func... | MODIFY | Summary: IPI: Drk interaction with the Ack non-receptor tyrosine kinase. Reason: The source supports a specific interaction between Drk and the Ack tyrosine-kinase signaling module. Protein tyrosine kinase binding is the more informative molecular-function term. Proposed replacements: protein tyrosine kinase binding Supporting Evidence: PMID:22615583 Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. |
| GO:0005515 protein binding | IPI PMID:35952612 Insight into the C-terminal SH3 domain mediated binding of D... | MODIFY | Summary: IPI: Drk-Sos binding captured as generic protein binding. Reason: NMR binding data show Drk SH3-domain recognition of Sos proline-rich motifs; replace generic protein binding with proline-rich region binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:35952612 Sos-derived two peptides with PxxPxR motif showed stronger affinity to Drk-CSH3, indicating that the Sos PRMs can bind both N- and C-SH3 domains. Dos-derived two peptides could also bind Drk-CSH3 |
| GO:0005515 protein binding | IPI PMID:35952612 Insight into the C-terminal SH3 domain mediated binding of D... | MODIFY | Summary: IPI: Drk-Dos binding captured as generic protein binding. Reason: Dos peptide binding by Drk-CSH3 is SH3 recognition of Dos proline-rich motifs, so the row should use GO:0070064 rather than the uninformative parent GO:0005515. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:35952612 Sos-derived two peptides with PxxPxR motif showed stronger affinity to Drk-CSH3, indicating that the Sos PRMs can bind both N- and C-SH3 domains. Dos-derived two peptides could also bind Drk-CSH3 |
| GO:0005515 protein binding | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | MODIFY | Summary: IPI: Drk-Sos binding captured as generic protein binding. Reason: The experiment supports Drk binding to the Sos tail through Drk SH3 domains; proline-rich region binding is the specific Drk molecular activity demonstrated. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:7781603 Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. |
| GO:0005515 protein binding | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | MODIFY | Summary: IPI: Drk-Sevenless binding captured as generic protein binding. Reason: The supporting entity is Sevenless and the biology is Drk SH2-domain recruitment to Sev, so sevenless binding is a more informative replacement term than generic protein binding. Proposed replacements: sevenless binding Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0005515 protein binding | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | MODIFY | Summary: IPI: Drk-Sos binding captured as generic protein binding. Reason: The cited paper established that the Sos C-terminal tail binds Drk SH3 domains; the right specific activity is proline-rich region binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0005515 protein binding | IPI PMID:9178769 D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene,... | UNDECIDED | Summary: IPI: Drk-Sos protein-binding row from the D-Cbl study. Reason: The cached abstract is about D-Cbl and explicitly says the shorter D-Cbl isoform cannot bind SH3-domain adaptors including Drk; the full text is unavailable here and the abstract does not expose the Sos-specific IPI experiment, so this row is deferred rather than removed. Supporting Evidence: PMID:9178769 D-Cbl is C-terminally truncated relative to c-Cbl and SLI-1 and consequently is unable to bind SH3-domain containing adaptor proteins, including the Drosophila Grb2 homologue, Drk. |
| GO:0005515 protein binding | IPI PMID:9671493 Disabled is a putative adaptor protein that functions during... | MODIFY | Summary: IPI: Drk-Dab binding captured as generic protein binding. Reason: Disabled binds the Drk SH3 domains through a proline-rich region during Sevenless signaling; GO:0070064 captures the domain-level recognition more precisely than protein binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:9671493 DAB binds to the SH3 domains of DRK. DAB and DRK form a complex in vivo that appears to be distinct from the DRK-SOS complex. |
| GO:0005654 nucleoplasm | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | KEEP AS NON CORE | Summary: HDA: CPTI YFP-trap localization of Drk to nuclei in cellularizing embryos. Reason: The YFP-trap screen reports prominent nuclear localization for Drk. This is retained as an observed localization but is not the canonical RTK adaptor site of action. Supporting Evidence: PMID:25294944 Other lines tag two kinases CaMKII (CPTI-000944) and Drk (CPTI-002249, note that the main localisation is in nuclei). |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: Drk inferred to be active in the nucleoplasm. Reason: The family has nuclear/nucleoplasmic localization evidence and fly Drk itself was observed with a predominantly nuclear CPTI protein trap. This is plausible but peripheral to the cytosolic and membrane RTK-adaptor role. Supporting Evidence: PMID:25294944 Other lines tag two kinases CaMKII (CPTI-000944) and Drk (CPTI-002249, note that the main localisation is in nuclei). |
| GO:0005737 cytoplasm | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: HDA: CPTI YFP-trap localization of Drk in the cytoplasm. Reason: A cytoplasmic pool is expected for a receptor-proximal adaptor that is recruited to activated membrane receptors, and the protein-trap screen observed non-nuclear Drk puncta as well as a major nuclear signal. Supporting Evidence: PMID:25294944 Other lines tag two kinases CaMKII (CPTI-000944) and Drk (CPTI-002249, note that the main localisation is in nuclei). |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytoplasmic Drk/GRB2-family activity. Reason: The inference is consistent with Drk acting as a soluble cytoplasmic SH2/SH3 adaptor that is recruited to activated RTKs and scaffolds. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: plasma-membrane activity of the GRB2/Sem-5/DRK adaptor family. Reason: Activated RTKs recruit Drk to the cytoplasmic face of the plasma membrane, and this membrane recruitment is central to linking receptor phosphorylation to Ras activation. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0005886 plasma membrane | IDA PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IDA: Drk localization to the plasma membrane upon RTK activation. Reason: The original Drk study explicitly coupled activated RTK binding with Drk localization to the plasma membrane, supporting this cellular-component assertion. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: signal transduction. Reason: Although broad, this term is accurate for Drk: it is a conserved adaptor that transduces signals from activated receptor tyrosine kinases to Sos/Ras/MAPK. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: IEA/ARBA: epidermal growth factor receptor signaling pathway. Reason: The electronic call is consistent with direct fly evidence that secreted Spitz activates DER, which associates with Drk and triggers MAP kinase activation. Supporting Evidence: PMID:7601354 Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:16326394 Distinct roles for two receptor tyrosine kinases in epitheli... | ACCEPT | Summary: IMP: Drk in EGFR signaling during dorsal air-sac growth. Reason: The air-sac phenotype is a developmental context of the same Drk-dependent DER/EGFR signaling module directly supported in other fly assays; keep this duplicate EGFR-pathway row with the other accepted EGFR signaling annotations. Supporting Evidence: PMID:16326394 Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival |
| GO:0007173 epidermal growth factor receptor signaling pathway | IMP PMID:8162856 The sevenless signalling cassette mediates Drosophila EGF re... | ACCEPT | Summary: IMP: Drk in the DER/EGFR signaling cassette. Reason: Clonal analysis placed Drk with Sos, Ras1, Raf and rolled/MAPK in the cassette that mediates DER signaling during epidermal development. Supporting Evidence: PMID:8162856 It appears that these components form a signalling cassette, which mediates all aspects of DER signalling |
| GO:0007173 epidermal growth factor receptor signaling pathway | IPI PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: IPI: DER/EGFR association with Drk after Spitz stimulation. Reason: Secreted Spitz induces DER autophosphorylation, DER-Drk association and MAPK activation in Drosophila cells, which directly supports Drk participation in the EGFR pathway. Supporting Evidence: PMID:7601354 Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. |
| GO:0007265 Ras protein signal transduction | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Drk participation in Ras protein signal transduction through Sos recruitment. Reason: Drk recruits the Ras GEF Sos through its SH3 domains to couple activated RTKs to Ras; this is the central downstream output of Drk. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0007265 Ras protein signal transduction | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Drk participation in RTK-to-Ras signaling. Reason: The row duplicates the core mechanism in which Drk binds activated RTKs and Sos to drive Ras activation. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0007426 tracheal outgrowth, open tracheal system | IMP PMID:16326394 Distinct roles for two receptor tyrosine kinases in epitheli... | KEEP AS NON CORE | Summary: IMP: tracheal outgrowth in the dorsal air-sac FGFR/EGFR model. Reason: Tracheal outgrowth is a tissue-level branch-morphogenesis output downstream of RTK/Ras/MAPK signaling; it is a valid developmental role but not the core molecular function of Drk. Supporting Evidence: PMID:16326394 Fgf signaling requires Ras, the Mapk pathway, and Pointed to direct migration |
| GO:0007427 epithelial cell migration, open tracheal system | IMP PMID:16326394 Distinct roles for two receptor tyrosine kinases in epitheli... | KEEP AS NON CORE | Summary: IMP: epithelial migration during dorsal air-sac outgrowth. Reason: FGF-directed cell migration in the air sac is a specific developmental use of the RTK/Ras/MAPK module containing Drk, so it is kept as non-core. Supporting Evidence: PMID:16326394 Fgf signaling directs cell migration at the tip of the structure |
| GO:0007465 R7 cell fate commitment | IGI PMID:19083999 SOCS36E specifically interferes with Sevenless signaling dur... | KEEP AS NON CORE | Summary: IGI: R7 cell fate commitment downstream of Sevenless. Reason: R7 specification is a classic Sevenless pathway output of Drk-mediated Ras/MAPK signaling. It is well supported but is a fly eye developmental endpoint rather than Drk's general adaptor activity. Supporting Evidence: PMID:19083999 Overexpression of Socs36E strongly suppresses the specification of extra R7 photoreceptor cells in response to constitutive activation of Sev |
| GO:0007465 R7 cell fate commitment | IGI PMID:20980384 Competition between SOCS36E and Drk modulates Sevenless rece... | KEEP AS NON CORE | Summary: IGI: R7 specification modulated by direct competition for Sevenless binding. Reason: The paper supports a direct Drk-Sev interaction and its positive effect on the Ras/MAPK burst needed for R7 fate; keep as a Sevenless developmental output. Supporting Evidence: PMID:20980384 demonstrate that Sev binds directly to either the suppressor protein SOCS36E or the adaptor protein Drk. |
| GO:0007465 R7 cell fate commitment | IGI PMID:8462097 An SH3-SH2-SH3 protein is required for p21Ras1 activation an... | KEEP AS NON CORE | Summary: IGI: R7 cell fate commitment through the Sevenless/Drk/Sos axis. Reason: Genetic evidence identifies Drk as a rate-limiting component downstream of Sev for R7 development. This is a specific eye-fate output of the core RTK adaptor role. Supporting Evidence: PMID:8462097 An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. |
| GO:0007476 imaginal disc-derived wing morphogenesis | IMP PMID:16648592 Epidermal growth factor receptor and transforming growth fac... | KEEP AS NON CORE | Summary: IMP: wing-shape effects from reduced RTK-network gene dosage. Reason: The quantitative wing screen supports a heterozygous developmental phenotype for RTK-network components including drk. Wing morphogenesis is retained as a peripheral developmental output. Supporting Evidence: PMID:16648592 Using geometric morphometric methods, it is shown that the majority of these mutations have profound effects on shape but not size of the wing when measured as heterozygotes. |
| GO:0007605 sensory perception of sound | IDA PMID:30610177 Dysfunction of GRAP, encoding the GRB2-related adaptor prote... | KEEP AS NON CORE | Summary: IDA: drk requirement in the fly auditory organ. Reason: Loss of drk in Johnston's organ causes scolopidial defects and behavioral deficits. This supports a sensory-neuron role, but not a separate biochemical activity from adaptor signaling. Supporting Evidence: PMID:30610177 the loss of drk in JO causes scolopidium abnormalities |
| GO:0007614 short-term memory | IMP PMID:19244537 A dual role for the adaptor protein DRK in Drosophila olfact... | KEEP AS NON CORE | Summary: IMP: short-term memory defects in drk heterozygotes. Reason: Drk is acutely required in mushroom-body neurons for efficient learning and memory; this behavioral output is downstream of the same Ras/Raf/MAPK signaling logic and is non-core. Supporting Evidence: PMID:19244537 drk mutant heterozygotes exhibit deficits in olfactory learning and memory |
| GO:0008180 COP9 signalosome | IBA GO_REF:0000033 | REMOVE | Summary: IBA: COP9 signalosome membership. Reason: COP9 signalosome is a defined COPS1-8/GPS1 complex and is not a GRB2/Sem-5/DRK SH2/SH3 adaptor complex. This appears to be an over-propagated family inference and is removed. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN005273574 · GRB2/Sem-5/DRK family node SUPPORTS SOURCE BUT NOT TARGET Drk/GRB2 proteins are receptor-proximal SH2/SH3 adaptors, not stable subunits of the COPS1-8 COP9 signalosome. |
| GO:0008286 insulin receptor signaling pathway | IPI PMID:26119340 The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longe... | UNDECIDED | Summary: IPI: insulin-receptor-pathway row supported by a Chico interaction. Reason: Drk can plausibly link multiple RTKs and insulin-pathway adaptors to Ras/ERK, but the cached abstract for this paper only exposes Ras-Erk-ETS aging downstream of reduced IIS and not the Drk-Chico IPI evidence. Deferred pending full-text confirmation. Supporting Evidence: PMID:26119340 Here, we identify a critical role for Ras-Erk-ETS signaling in aging in Drosophila. |
| GO:0008293 torso signaling pathway | IDA PMID:9885560 Opposing actions of CSW and RasGAP modulate the strength of ... | ACCEPT | Summary: IDA: Drk in the Torso RTK pathway. Reason: Corkscrew links Torso to Drk binding, physically connecting the Torso receptor to Ras activation; Torso signaling is a direct Drk RTK pathway. Supporting Evidence: PMID:9885560 CSW also serves as an adaptor protein for DRK binding, physically linking Torso to Ras activation. |
| GO:0008293 torso signaling pathway | IGI PMID:10882065 The Drosophila SHC adaptor protein is required for signaling... | ACCEPT | Summary: IGI: parallel adaptor input from Dos, Drk and Shc in Torso signaling. Reason: Double-mutant analysis showed that DOS, DRK and DSHC act in parallel in Torso signal transduction, so the annotation is sound. Supporting Evidence: PMID:10882065 We show by double-mutant analysis that the adaptors DOS, DRK, and DSHC act in parallel to transduce the Torso signal. |
| GO:0008293 torso signaling pathway | IMP PMID:7720074 The torso receptor tyrosine kinase can activate Raf in a Ras... | ACCEPT | Summary: IMP: drk assayed in the Torso-to-Raf pathway. Reason: The abstract emphasizes a Ras-independent Raf input, but it also places drk in the Torso RTK analysis. Given independent Torso evidence for Drk, this duplicate Torso-pathway row is retained with the other accepted Torso signaling annotations. Supporting Evidence: PMID:7720074 analysis of D-Raf activation in the absence of either the exchange factor Son of sevenless (Sos) or the adaptor protein drk (Grb2) |
| GO:0008306 associative learning | IMP PMID:19244537 A dual role for the adaptor protein DRK in Drosophila olfact... | KEEP AS NON CORE | Summary: IMP: Drk in mushroom-body short-term memory. Reason: The learning and memory phenotypes establish a neuronal role for Drk, downstream of Ras/MAPK regulation, but this is a specialized output. Supporting Evidence: PMID:19244537 The data establish a role for DRK in Drosophila behavioral neuroplasticity |
| GO:0008355 olfactory learning | IMP PMID:19244537 A dual role for the adaptor protein DRK in Drosophila olfact... | KEEP AS NON CORE | Summary: IMP: Drk in olfactory learning. Reason: Drk is required acutely in mushroom-body neurons for efficient olfactory learning; retain the behavioral term as non-core. Supporting Evidence: PMID:19244537 the protein is required acutely within mushroom body neurons to mediate efficient learning |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IMP PMID:16326394 Distinct roles for two receptor tyrosine kinases in epitheli... | KEEP AS NON CORE | Summary: IMP: FGFR signaling in air-sac branch morphogenesis. Reason: FGFR signaling uses Ras/MAPK to drive air-sac migration. This is a specific RTK pathway context for Drk rather than its general molecular activity. Supporting Evidence: PMID:16326394 Fgf signaling requires Ras, the Mapk pathway, and Pointed to direct migration |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA/ARBA: anatomical structure morphogenesis. Reason: This is a very broad developmental ancestor of several Drk RTK-signaling phenotypes. The term is not false, but it loses pathway specificity and should not be emphasized as a Drk function. |
| GO:0016020 membrane | EXP PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: EXP: membrane localization from the original Drk study. Reason: Membrane localization is broad but correct for a peripheral adaptor that is recruited to activated receptor tyrosine kinases; the seeded plasma-membrane row already captures the more specific site. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA: UniProt SubCell membrane mapping. Reason: Drk is a peripheral cytosolic adaptor recruited to activated membrane receptors; the broad membrane mapping is correct, while the experimental row captures the more specific plasma membrane location. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:12128212 SH3 domain-mediated binding of the Drk protein to Dos is an ... | ACCEPT | Summary: IPI: Drk adaptor activity between Sev and Dos/Csw. Reason: Drk links activated Sev to the Dos multi-site adaptor via SH2 and SH3 interactions; this is a direct example of signaling receptor complex adaptor activity. Supporting Evidence: PMID:12128212 Drk binds with its SH2 domain to the autophosphorylated Sev receptor while the C-terminal SH3 domain is able to associate with Dos. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:7601354 Secreted Spitz triggers the DER signaling pathway and is a l... | ACCEPT | Summary: IPI: Drk adaptor activity downstream of Drosophila EGFR. Reason: DER/EGFR autophosphorylation recruits Drk and is followed by MAPK activation, matching the receptor-complex adaptor role. Supporting Evidence: PMID:7601354 Following autophosphorylation, DER associates with the Drk adapter protein. Consequently, activation of MAP kinase is observed. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:7781603 Biochemical and genetic analysis of the Drk SH2/SH3 adaptor ... | ACCEPT | Summary: IPI: Drk adaptor activity linking Sevenless to Sos. Reason: The Drk SH2/SH3 architecture links activated Sev to Sos and Ras activation; this is the canonical receptor-complex adaptor function. Supporting Evidence: PMID:7781603 Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Drk receptor-complex adaptor activity through Sos. Reason: Direct Sos binding by Drk SH3 domains is the effector-binding side of Drk adaptor activity. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0030159 signaling receptor complex adaptor activity | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Drk receptor-complex adaptor activity through Sevenless. Reason: Drk binds autophosphorylated Sevenless through its SH2 domain to recruit Sos through its SH3 domains, coupling the receptor to Ras. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0030707 follicle cell of egg chamber development | IMP PMID:26205122 A large-scale in vivo RNAi screen to identify genes involved... | MARK AS OVER ANNOTATED | Summary: IMP: follicle-cell differentiation phenotype from an in vivo RNAi screen. Reason: The screen implicated drk in Cut expression during the Notch-regulated mitotic/endocycle switch, but this high-throughput follicle-cell readout is distant from Drk's direct RTK adaptor activity. Supporting Evidence: PMID:26205122 We screened 2205 RNAi lines and found 33 genes regulating Cut expression during the M/E switch. |
| GO:0032991 protein-containing complex | IDA PMID:22615583 Drosophila activated Cdc42 kinase has an anti-apoptotic func... | REMOVE | Summary: IDA: generic protein-containing complex from the Ack interaction study. Reason: The Ack paper identified Drk as an Ack-interacting protein, but this broad cellular-component term does not describe a defined complex and adds no functional information beyond the interaction itself. Supporting Evidence: PMID:22615583 Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. |
| GO:0043408 regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: regulation of MAPK cascade. Reason: Recruitment of Sos by Drk is a conserved upstream step that promotes Ras and then MAPK cascade activation downstream of RTKs. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0045202 synapse | EXP PMID:30610177 Dysfunction of GRAP, encoding the GRB2-related adaptor prote... | KEEP AS NON CORE | Summary: EXP: synaptic localization in fly neurons. Reason: The hearing-loss study localized Drk with synapsin at neuronal synapses. This localization is retained but is secondary to the broadly conserved RTK adaptor activity. Supporting Evidence: PMID:30610177 drk specifically colocalizes with synapsin at synapses |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA: UniProt SubCell synapse mapping. Reason: Consistent with direct Drk/synapsin colocalization in neurons; kept as a non-core neuronal localization. Supporting Evidence: PMID:30610177 drk specifically colocalizes with synapsin at synapses |
| GO:0045500 sevenless signaling pathway | IDA PMID:20980384 Competition between SOCS36E and Drk modulates Sevenless rece... | ACCEPT | Summary: IDA: Sevenless signaling pathway. Reason: Direct competition between Drk and SOCS36E for Sevenless binding modulates Sev activity, supporting Drk as a positive Sev-pathway component. Supporting Evidence: PMID:20980384 demonstrate that Sev binds directly to either the suppressor protein SOCS36E or the adaptor protein Drk. |
| GO:0045500 sevenless signaling pathway | IGI PMID:19083999 SOCS36E specifically interferes with Sevenless signaling dur... | ACCEPT | Summary: IGI: Sevenless signaling attenuated by SOCS36E competition with Drk. Reason: SOCS36E genetic interactions probe a Drk-dependent Sev/MAPK signal during R7 specification; the Sev pathway assignment is correct. Supporting Evidence: PMID:19083999 Socs36E constitutes a novel partially redundant feedback mechanism that contributes to the robustness of R7 specification |
| GO:0045500 sevenless signaling pathway | IGI PMID:7781603 Biochemical and genetic analysis of the Drk SH2/SH3 adaptor ... | ACCEPT | Summary: IGI: Drk in Sevenless signaling. Reason: Biochemical and genetic evidence places Drk downstream of Sev and upstream of Sos/Ras in the developing eye. Supporting Evidence: PMID:7781603 Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. |
| GO:0045500 sevenless signaling pathway | IGI PMID:8462097 An SH3-SH2-SH3 protein is required for p21Ras1 activation an... | ACCEPT | Summary: IGI: Drk is required for Sevenless signaling. Reason: The original drk study showed that Drk, Ras1 and Sos are required for sevenless signaling and that Drk can bridge activated RTKs to Sos. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0045500 sevenless signaling pathway | IGI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IGI: Sevenless signaling through Drk-Sev interaction. Reason: Genetic analysis and biochemical receptor binding support Drk function in Sev signaling. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0045500 sevenless signaling pathway | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Sevenless pathway output of the Drk-Sos interaction. Reason: Sos binding is how Drk couples the Sevenless receptor complex to Ras activation, so this IPI row correctly connects Drk to the Sev pathway. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0045500 sevenless signaling pathway | IPI PMID:8462098 A Drosophila SH2-SH3 adaptor protein implicated in coupling ... | ACCEPT | Summary: IPI: Sevenless pathway output of Drk-Sevenless binding. Reason: Drk binding to activated Sevenless is a receptor-proximal step in Sev signaling. Supporting Evidence: PMID:8462098 These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. |
| GO:0045793 positive regulation of cell size | IMP PMID:19216764 PDGF/VEGF signaling controls cell size in Drosophila. | KEEP AS NON CORE | Summary: IMP: reduced cell size after drk RNAi in Pvr/Ras growth signaling. Reason: drk was one of the Ras-pathway hits in a cultured-cell size screen. This supports a Pvr/Ras growth phenotype, but positive regulation of cell size is a cell-culture output rather than the core Drk activity. Supporting Evidence: PMID:19216764 this screen identified a novel role for autocrine signaling through Pvfs and the receptor tyrosine kinase Pvr in the control of the autonomous growth of Drosophila cells in culture |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IDA PMID:23878397 Platelet-derived growth factor/vascular endothelial growth f... | KEEP AS NON CORE | Summary: IDA: PVR/PDGF-VEGF receptor signaling through Drk. Reason: PVR uses Drk to sustain ERK and TORC1 in cultured insect cells. This is a real RTK input, but less central for Drk than the general RTK-to-Sos/Ras adaptor function. Supporting Evidence: PMID:23878397 Drk knockdown markedly downregulated P-S6K and P-ERK |
| GO:0048010 vascular endothelial growth factor receptor signaling pathway | IMP PMID:19216764 PDGF/VEGF signaling controls cell size in Drosophila. | KEEP AS NON CORE | Summary: IMP: Pvr/Ras cell-size pathway from an RNAi screen. Reason: The Pvr/Ras pathway controls S2R+ cell size in culture and drk is a top Ras-pathway hit; the more direct PVR study confirms that Drk transduces PVR to ERK/TORC1. Supporting Evidence: PMID:19216764 Pvr/Ras signaling also affected the size of other Drosophila cell lines and of larval hemocytes |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IGI PMID:21340027 D-Cbl binding to Drk leads to dose-dependent down-regulation... | KEEP AS NON CORE | Summary: IGI: Drk and D-CblL cooperate to promote EGFR ligand-receptor endocytosis. Reason: This row captures a specific attenuation branch in which Drk binds D-CblL and helps down-regulate Gurken/EGFR by endocytosis; it is retained as a non-core regulatory output. Supporting Evidence: PMID:21340027 Drk facilitates the dose-dependent regulation of EGFR signaling through binding to the proline-rich motif of D-CblL, PR. |
| GO:0048468 cell development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA/ARBA: cell development. Reason: The assertion is only a broad ancestor of multiple tissue-specific Drk phenotypes and should be represented, when needed, by the specific RTK pathways rather than a generic developmental process term. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IMP PMID:23878397 Platelet-derived growth factor/vascular endothelial growth f... | ACCEPT | Summary: IMP: Drk promotes ERK activation downstream of PVR. Reason: Drk knockdown reduces P-ERK downstream of PVR, matching the canonical Drk/GRB2 role of linking RTKs to Ras/ERK. Supporting Evidence: PMID:23878397 Drk knockdown markedly downregulated P-S6K and P-ERK |
| GO:0098793 presynapse | IDA PMID:30610177 Dysfunction of GRAP, encoding the GRB2-related adaptor prote... | KEEP AS NON CORE | Summary: IDA: Drk at the presynapse. Reason: Drk colocalizes with synapsin at neuronal synapses, supporting a presynaptic localization in the auditory-organ study. Supporting Evidence: PMID:30610177 drk specifically colocalizes with synapsin at synapses |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: IEA/ARBA: animal gross anatomical part developmental process. Reason: This ARBA term is a very broad developmental roll-up of Drk phenotypes. It is not a useful direct functional annotation for a receptor-proximal adaptor. |
| GO:1904263 positive regulation of TORC1 signaling | IMP PMID:23878397 Platelet-derived growth factor/vascular endothelial growth f... | KEEP AS NON CORE | Summary: IMP: Drk is required for TORC1 activation downstream of PVR. Reason: PVR signals through Drk and Ras85D to activate TORC1 as well as ERK; this is a well-supported PVR-context output of Drk adaptor signaling. Supporting Evidence: PMID:23878397 Drk knockdown markedly downregulated P-S6K and P-ERK |
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Download this section (compressed HTML)downstream of receptor kinase (drk) encodes an adaptor protein that recognizes phosphorylated tyrosine residues of membrane receptors and triggers the Ras/Raf/MAPK pathway. drk product contributes to the regulation of cytoskeletal organization and participates in developmental and cognitive processes (associative learning, anesthesia resistant memory).
Provider deep research was unavailable in this pass: Falcon required agentapi on PATH, and the Perplexity/OpenAI fallbacks had no API keys in the parent environment. The annotation review therefore relied on the seeded UniProt and GOA data, cached PMID records under publications/, and the local GO-CAM cache for Drosophila EGFR and Torso pathway models.
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