The immune deficiency (Imd) pathway is the main Drosophila defense against Gram-negative bacteria and some Gram-positive bacilli. It is triggered when DAP-type peptidoglycan binds the transmembrane receptor PGRP-LC or the intracellular receptor PGRP-LE. The receptors recruit the death-domain protein Imd, which assembles a complex with the adaptor Fadd and the caspase Dredd. Dredd cleaves Imd, and the E3 ligase Diap2, with the E2 enzymes Bendless and Effete and the E2 variant Uev1A, attaches K63-linked ubiquitin chains. These chains recruit the Tak1-Tab2 kinase complex, which activates the IKK complex (IKKbeta and Kenny). IKK phosphorylates the NF-kappa-B factor Relish, Dredd cleaves it, and the Rel homology domain enters the nucleus to induce antimicrobial peptide genes. Tak1 also activates the JNK branch (Hemipterous, Basket) that acts through AP-1 (Jra, Kayak).
Boundary. Core components only (FlyBase IMD-C). IKKbeta and Relish are shared with cGAS-STING signaling, and the JNK cascade is shared with JNK signaling. Amidase PGRPs, Pirk, Caspar, deubiquitinases and other FlyBase regulators are not parts. Tak1-Tab2 is emitted as a complex without a GO complex term. FlyBase groups realized by this module: IMD (FBgg0001194). Subgroups folded into it: IMD-C. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: IMD-N (negative regulators of imd signaling pathway, 45 genes); IMD-P (positive regulators of imd signaling pathway, 19 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_imd_signaling.yaml. Member genes with a gene review in this repository: Diap2, IKKbeta, Rel.
All recommended fields populated.
✗ none found
No MODULE:dmel_imd_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.
2 gene-function check(s) reflected in core functions · 0 conflict(s) · 9 evidence or coverage gap(s) (12 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 |
|---|---|---|---|
| pgrp_receptors_pgrp_lc | PGRP-LC UniProtKB:Q9GNK5 Gene |
peptidoglycan immune receptor activity GO:0016019 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| pgrp_receptors_pgrp_le | PGRP-LE UniProtKB:Q9VXN9 Gene |
peptidoglycan immune receptor activity GO:0016019 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| imd_fadd_dredd_dredd | Dredd UniProtKB:Q8IRY7 Gene |
cysteine-type endopeptidase activity GO:0004197 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| imd_ubiquitination_diap2 | Diap2 UniProtKB:Q24307 Gene |
ubiquitin protein ligase activity GO:0061630 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| imd_ubiquitination_ben | ben UniProtKB:P35128 Gene |
ubiquitin conjugating enzyme activity GO:0061631 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| imd_ubiquitination_eff | eff UniProtKB:P25867 Gene |
ubiquitin conjugating enzyme activity GO:0061631 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| tak1_tab2_complex/tak1 | Tak1 UniProtKB:Q9V3Q6 Complex Unit |
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. |
| ikk_complex_complex/ikkbeta | IKKbeta UniProtKB:Q9VEZ5 Complex Unit |
IkappaB kinase activity GO:0008384 |
Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it. |
| relish_rel | Rel UniProtKB:Q94527 Gene |
DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| jnk_kinases_hep | hep UniProtKB:Q23977 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_kinases_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. |
| ap1_complex | PROTEIN_COMPLEX Gene |
DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
2 complete review(s) · 3 with deep research · 16 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Tab2 A0A0B4KG87 | ✗ | — | — |
| Diap2 Q24307 | ✓ | 54/67 | ✓ |
| IKKbeta Q9VEZ5 | ✓ | ✓ | ✓ |
| Jra P18289 | ✗ | — | — |
| kay P21525 | ✗ | — | — |
| eff P25867 | ✗ | — | — |
| ben P35128 | ✗ | — | — |
| bsk P92208 | ✗ | — | — |
| hep Q23977 | ✗ | — | — |
| imd Q7K4Z4 | ✗ | — | — |
| Dredd Q8IRY7 | ✗ | — | — |
| foxo Q95V55 | ✗ | — | — |
| PGRP-LC Q9GNK5 | ✗ | — | — |
| key Q9GYV5 | ✗ | — | — |
| Fadd Q9V3B4 | ✗ | — | — |
| Tak1 Q9V3Q6 | ✗ | — | — |
| Uev1A Q9VRL1 | ✗ | — | — |
| PGRP-LE Q9VXN9 | ✗ | — | — |
| Rel Q94527 | ✓ | ✓ | ✓ |
Peptidoglycan sensing by PGRP-LC/LE activates Imd, Fadd and Dredd, Tak1 and the IKK complex, leading to Relish-dependent antimicrobial peptide expression and a JNK/AP-1 branch.
Diap2 is the E3 ligase; Bendless (Ubc13) with the non-catalytic variant Uev1A, and Effete, are the E2 enzymes.
FOXO is listed by FlyBase as a core component; it can induce antimicrobial peptide genes, and its position relative to the canonical Imd cascade is not resolved.