Eiger is the single Drosophila member of the tumor necrosis factor superfamily. It is a type II transmembrane protein that can be released as a soluble ligand by the metalloprotease Tace. Eiger binds the TNF receptors Grindelwald and Wengen, which signal through Traf proteins and the Tak1-Tab2 kinase complex to the JNK kinase kinases Hemipterous and Mkk4 and the JNK Basket. The Ste20-family kinase Misshapen acts upstream in the JNK cascade. JNK activation by Eiger induces apoptosis and cell elimination in development and tumour suppression, and also contributes to tissue growth, regeneration, pain sensitization and immune responses.
Boundary. The module stops at the JNK Basket; the AP-1 transcription factors (Jra, Kay) and JNK target genes are not FlyBase members of this group and are left out. Licorne (MKK3) belongs to the p38 branch and is included because FlyBase lists it among the core components. Traf6 is also in the FlyBase positive regulator set; Traf4 is not a FlyBase member, although it has been implicated in Eiger signaling. The JNK phosphatase Puckered and other regulators are FlyBase regulator sets and not parts. FlyBase groups realized by this module: TNF (FBgg0001560). Subgroups folded into it: TNF-C. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: TNF-N (negative regulators of tnfalpha-eiger signaling pathway, 5 genes); TNF-P (positive regulators of tnfalpha-eiger signaling pathway, 7 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_eiger_tnf_signaling.yaml. Member genes with a gene review in this repository: Tace.
All recommended fields populated.
✗ none found
No MODULE:dmel_eiger_tnf_signaling deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
1 gene-function check(s) reflected in core functions · 0 conflict(s) · 7 evidence or coverage gap(s) (8 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.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| eiger_shedding_tace | Tace UniProtKB:Q9VAC5 Gene |
metalloendopeptidase activity GO:0004222 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| eiger_ligand_egr | egr UniProtKB:Q8MUJ1 Gene |
tumor necrosis factor receptor binding GO:0005164 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| traf_tak1_relay_tak1 | Tak1 UniProtKB:Q9V3Q6 Gene |
MAP kinase kinase kinase activity GO:0004709 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| traf_tak1_relay_msn | msn UniProtKB:Q9W002 Gene |
MAP kinase kinase kinase kinase activity GO:0008349 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| mapkk_tier_hep | hep UniProtKB:Q23977 Gene |
JUN kinase kinase activity GO:0008545 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| mapkk_tier_mkk4 | Mkk4 UniProtKB:O61444 Gene |
JUN kinase kinase activity GO:0008545 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| mapkk_tier_lic | lic UniProtKB:O62602 Gene |
MAP kinase kinase activity GO:0004708 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| jnk_bsk | bsk UniProtKB:P92208 Gene |
JUN kinase activity GO:0004705 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
1 complete review(s) · 1 with deep research · 11 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Tab2 A0A0B4KG87 | ✗ | — | — |
| Mkk4 O61444 | ✗ | — | — |
| lic O62602 | ✗ | — | — |
| bsk P92208 | ✗ | — | — |
| hep Q23977 | ✗ | — | — |
| egr Q8MUJ1 | ✗ | — | — |
| Tak1 Q9V3Q6 | ✗ | — | — |
| grnd Q9VJ83 | ✗ | — | — |
| wgn Q9VWS4 | ✗ | — | — |
| msn Q9W002 | ✗ | — | — |
| Traf6 Q9W3I9 | ✗ | — | — |
| Tace Q9VAC5 | ✓ | ✓ | ✓ |
TNF-like ligand Eiger and its receptors Grindelwald and Wengen, which activate JNK through Traf6, Tak1-Tab2 and the JNK kinase kinases Hep and Mkk4.
Traf6 and the Tak1-Tab2 complex relay receptor signals to the MAP kinase kinase kinase Tak1; the MAP4K Misshapen also acts upstream of the JNK kinase kinases.