Sevenless receptor tyrosine kinase signaling in Drosophila melanogaster

Sevenless is a receptor tyrosine kinase expressed in a subset of cells of the developing eye that is required for the R7 photoreceptor to adopt its fate. It is activated by Bride of sevenless, a seven-pass transmembrane ligand on the neighbouring R8 cell. The activated receptor recruits the adaptor Drk (Grb2), the docking protein Daughter of sevenless and the tyrosine phosphatase Corkscrew, which together activate Son of sevenless and Ras. Ras drives the Raf-MEK (Dsor1)-ERK (Rolled) cascade, aided by the scaffolds Ksr and Cnk. ERK phosphorylates the ETS factors Pointed (activating it) and Yan/Aop (relieving its repression), and induces Phyllopod, which with the E3 ligase Seven in absentia targets the repressor Tramtrack for degradation, allowing neuronal R7 differentiation.

MODULE:dmel_sevenless_signalingDRAFTCONCRETESignaling Pathwaymodules/dmel_sevenless_signaling.yaml
sevenless signaling pathwayGO:0045500 R7 cell fate commitmentGO:0007465
FB:FBgg0000941
FlyBase gene group SEVL: Sevenless signaling pathway
FlyBase release FB2026_03 groups 30 D. melanogaster genes as sevenless signaling pathway (SEVL); this module models that group.
GO:0045500
sevenless signaling pathway
GO term grounding the module as sevenless signaling pathway.
GO:0007465
R7 cell fate commitment
GO term grounding the module as R7 cell fate commitment.

Boundary. The Ras-ERK components are shared with other receptor tyrosine kinase pathways (EGFR, Torso, PVR); here they are the FlyBase Sevenless core components. Tramtrack is included as the substrate of the Phyllopod-Sina complex, as FlyBase places it among core components. FlyBase groups realized by this module: SEVL (FBgg0000941). Subgroups folded into it: SEVL-C. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: SEVL-P (positive regulators of sevenless signaling pathway, 8 genes); SEVL-N (negative regulators of sevenless signaling pathway, 5 genes). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_sevenless_signaling.yaml. Member genes with a gene review in this repository: drk, Dsor1, Raf, Ras85D, rl, Sos.

8Nodes
7Parts
0Variant Sets
0Variants
17Annotons
6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_sevenless_signaling deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 6 evidence or coverage gap(s) (11 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
sevenless_receptor_sev sev
UniProtKB:P13368
Gene 		transmembrane receptor protein tyrosine kinase activity
GO:0004714 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
sev_adaptors_csw csw
UniProtKB:P29349
Gene 		protein tyrosine phosphatase activity
GO:0004725 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ras_activation_sos Sos
UniProtKB:P26675
Gene 		guanyl-nucleotide exchange factor activity
GO:0005085 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ras_activation_ras85d Ras85D
UniProtKB:P08646
Gene 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mapk_cascade_raf Raf
UniProtKB:P11346
Gene 		MAP kinase kinase kinase activity
GO:0004709 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mapk_cascade_dsor1 Dsor1
UniProtKB:Q24324
Gene 		MAP kinase kinase activity
GO:0004708 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mapk_cascade_rl rl
UniProtKB:P40417
Gene 		MAP kinase activity
GO:0004707 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ets_factors_pnt pnt
UniProtKB:P51023
Gene 		DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ets_factors_aop aop
UniProtKB:Q01842
Gene 		DNA-binding transcription repressor activity, RNA polymerase II-specific
GO:0001227 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tramtrack_degradation_sina sina
UniProtKB:P21461
Gene 		ubiquitin protein ligase activity
GO:0061630 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tramtrack_degradation_ttk ttk
UniProtKB:P42282
Gene 		DNA-binding transcription repressor activity, RNA polymerase II-specific
GO:0001227 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Gene-review completeness (7/17 grounded genes reviewed)

2 complete review(s) · 5 with deep research · 10 missing review · 2 reviewed but lacking deep research

Gene Review Complete Deep research
cnk A1ZAS2 ✗ — —
boss P22815 ✓ 26/27 ✗
drk Q08012 ✓ 74/76 ✓
Dsor1 Q24324 ✓ ✓ ✓
sev P13368 ✗ — —
sina P21461 ✗ — —
csw P29349 ✗ — —
ttk P42282 ✗ — —
pnt P51023 ✗ — —
aop Q01842 ✗ — —
ksr Q24171 ✗ — —
phyl Q27934 ✗ — —
dos Q9VZZ9 ✗ — —
Raf P11346 ✓ 89/90 ✓
Ras85D P08646 ✓ ✓ ✓
rl P40417 ✓ 119/125 ✓
Sos P26675 ✓ 47/50 ✗

Details

Context
Drosophila melanogasterNCBITaxon:7227
Sevenless signaling pathwaySignaling Pathwaydmel_sevenless_signaling

Boss-activated Sevenless receptor tyrosine kinase pathway that signals through Ras-ERK, the ETS factors Pointed and Yan, and Phyllopod-Sina degradation of Tramtrack to specify the R7 photoreceptor.

sevenless signaling pathwayGO:0045500 R7 cell fate commitmentGO:0007465
Context
Drosophila melanogasterNCBITaxon:7227

Connections

boss_ligand -> sevenless_receptor Positively Regulates
Boss on R8 activates Sevenless on the R7 precursor.
sevenless_receptor -> sev_adaptors Positively Regulates
The activated receptor recruits Drk, Dos and Csw.
sev_adaptors -> ras_activation Positively Regulates
Drk recruits Sos, which activates Ras.
ras_activation -> mapk_cascade Positively Regulates
Ras-GTP activates Raf.
mapk_cascade -> ets_factors Positively Regulates
ERK activates Pointed and inactivates Yan.
mapk_cascade -> tramtrack_degradation Positively Regulates
ERK signaling induces phyllopod expression, leading to Sina-mediated Tramtrack degradation.
Part 1: ligand on R8
Bride of sevenlessSignaling Pathwayboss_ligand

Annotons

boss Bride of sevenless
boss_ligand_boss
Participant: Gene Product: boss
Gene Product:
bossUniProtKB:P22815
Part 2: receptor
Sevenless receptor tyrosine kinaseSignaling Pathwaysevenless_receptor

Annotons

sev Sevenless receptor tyrosine kinase
sevenless_receptor_sev
Participant: Gene Product: sev
Gene Product:
sevUniProtKB:P13368

Function

transmembrane receptor protein tyrosine kinase activityGO:0004714
Part 3: phosphotyrosine adaptors and docking proteins
Receptor-proximal adaptorsSignaling Pathwaysev_adaptors

Annotons

drk Receptor-proximal adaptors
sev_adaptors_drk
Participant: Gene Product: drk
Gene Product:
drkUniProtKB:Q08012
dos Receptor-proximal adaptors
sev_adaptors_dos
Participant: Gene Product: dos
Gene Product:
dosUniProtKB:Q9VZZ9
csw Receptor-proximal adaptors
sev_adaptors_csw
Participant: Gene Product: csw
Gene Product:
cswUniProtKB:P29349

Function

protein tyrosine phosphatase activityGO:0004725
Part 4: Ras activation
Sos and RasSignaling Pathwayras_activation

Annotons

Sos Sos and Ras
ras_activation_sos
Participant: Gene Product: Sos
Gene Product:
SosUniProtKB:P26675

Function

guanyl-nucleotide exchange factor activityGO:0005085
Ras85D Sos and Ras
ras_activation_ras85d
Participant: Gene Product: Ras85D
Gene Product:
Ras85DUniProtKB:P08646

Function

GTPase activityGO:0003924
Part 5: MAPK cascade
Raf-MEK-ERK cascade with scaffoldsSignaling Pathwaymapk_cascade

Annotons

Raf Raf-MEK-ERK cascade with scaffolds
mapk_cascade_raf
Participant: Gene Product: Raf
Gene Product:
RafUniProtKB:P11346

Function

MAP kinase kinase kinase activityGO:0004709

Processes

MAPK cascadeGO:0000165
ksr Raf-MEK-ERK cascade with scaffolds
mapk_cascade_ksr
Participant: Gene Product: ksr
Gene Product:
ksrUniProtKB:Q24171

Processes

MAPK cascadeGO:0000165
cnk Raf-MEK-ERK cascade with scaffolds
mapk_cascade_cnk
Participant: Gene Product: cnk
Gene Product:
cnkUniProtKB:A1ZAS2

Processes

MAPK cascadeGO:0000165
Dsor1 Raf-MEK-ERK cascade with scaffolds
mapk_cascade_dsor1
Participant: Gene Product: Dsor1
Gene Product:
Dsor1UniProtKB:Q24324

Function

MAP kinase kinase activityGO:0004708

Processes

MAPK cascadeGO:0000165
rl Raf-MEK-ERK cascade with scaffolds
mapk_cascade_rl
Participant: Gene Product: rl
Gene Product:
rlUniProtKB:P40417

Function

MAP kinase activityGO:0004707

Processes

MAPK cascadeGO:0000165
Part 6: transcriptional output
ETS transcription factors Pointed and YanSignaling Pathwayets_factors

Annotons

pnt ETS transcription factors Pointed and Yan
ets_factors_pnt
Participant: Gene Product: pnt
Gene Product:
pntUniProtKB:P51023

Function

DNA-binding transcription factor activity, RNA polymerase II-specificGO:0000981
aop ETS transcription factors Pointed and Yan
ets_factors_aop
Participant: Gene Product: aop
Gene Product:
aopUniProtKB:Q01842

Function

DNA-binding transcription repressor activity, RNA polymerase II-specificGO:0001227
Part 7: removal of the neuronal repressor Tramtrack
Phyllopod-Sina degradation of TramtrackSignaling Pathwaytramtrack_degradation

Annotons

phyl Phyllopod-Sina degradation of Tramtrack
tramtrack_degradation_phyl
Participant: Gene Product: phyl
Gene Product:
phylUniProtKB:Q27934
sina Phyllopod-Sina degradation of Tramtrack
tramtrack_degradation_sina
Participant: Gene Product: sina
Gene Product:
sinaUniProtKB:P21461

Function

ubiquitin protein ligase activityGO:0061630
ttk Phyllopod-Sina degradation of Tramtrack
tramtrack_degradation_ttk
Participant: Gene Product: ttk
Gene Product:
ttkUniProtKB:P42282

Function

DNA-binding transcription repressor activity, RNA polymerase II-specificGO:0001227