ERBB2/HER2 acts as a ligandless preferred dimerization partner for ERBB receptors, especially ERBB3 after neuregulin binding, producing potent PI3K-AKT and MAPK output.
Curated compact signaling-pathway module generated from verified UniProt exemplar accessions and local PAINT IBD rows. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther. Falcon integration (2026-06-28): Falcon findings are linked as evidence and family-level support. Automatically extracted open-question headings were intentionally not retained as knowledge_gap entries because they were not manually curated. Machine-generated Falcon citations remain curation support and are not manually adjudicated here.
All recommended fields populated.
✓ present
✓ 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) · 4 evidence or coverage gap(s) (5 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 |
|---|---|---|---|
| nrg1_nrg1_ligand | NRG1 UniProtKB:Q02297 Gene |
signaling receptor binding GO:0005102 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| erbb3_erbb3_co_receptor | ERBB3 UniProtKB:P21860 Family Representative |
neuregulin receptor activity (catalytically dead co-receptor) GO:0038131 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| erbb2_erbb2_receptor_kinase | ERBB2 UniProtKB:P04626 Family Representative |
transmembrane receptor protein tyrosine kinase activity GO:0004714 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| erbb3_erbb3_co_receptor | ERBB3 co-receptor family/ortholog group PANTHER:PTHR24416 Family |
neuregulin receptor activity (catalytically dead co-receptor) GO:0038131 |
Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0038131. |
| erbb2_erbb2_receptor_kinase | ERBB2 receptor kinase family/ortholog group PANTHER:PTHR24416 Family |
transmembrane receptor protein tyrosine kinase activity GO:0004714 |
Family Scope Restricted
GO:0004714 requires member-level assessment of residue site kinase_catalytic_triad; a family identifier does not establish that condition. Within the DDR clade the activity follows the kinase catalytic triad, which is kept everywhere except the dipteran Ddr node PTN002400510: Drosophila Ddr (Ala789, Ser897, Ser910) and Anopheles DDR fail the site and are predicted pseudokinases (not assayed). The PTN001230349 node assessment records the matching IKR recommendation. RESIDUE_DETERMINED means the term is true wherever the triad is intact; it is not the most specific term for vertebrate DDR1 and DDR2, whose reviews refine it to GO:0038062. |
2 complete review(s) · 2 with deep research · 2 missing review · 1 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| ERBB2 P04626 | ✓ | ✓ | ✗ |
| GRB2 P62993 | ✓ | ✓ | ✓ |
| ERBB3 P21860 | ✗ | — | — |
| PIK3R1 P27986 | ✓ | 413/415 | ✓ |
| NRG1 Q02297 | ✗ | — | — |
Neuregulin binding to ERBB3 promotes ERBB2-containing receptor dimers.
Curated exemplar for the nrg1 ligand role in ERBB2 signaling pathway.
Curated exemplar for the erbb3 co-receptor role in ERBB2 signaling pathway. ERBB3 is a pseudokinase; PAINT records the ancestral receptor tyrosine kinase activity as lost (IRD GO:0004714) at PTN002814617, and signalling output depends on heterodimerisation with a catalytically competent partner (ERBB2).
ERBB2 supplies the strong kinase-active partner in the receptor dimer.
Curated exemplar for the erbb2 receptor kinase role in ERBB2 signaling pathway.
ERBB2/ERBB3 phosphotyrosines recruit PI3K and adaptor proteins to drive growth and survival.
Curated exemplar for the pik3r1 p85 adaptor role in ERBB2 signaling pathway.
Curated exemplar for the grb2 adaptor role in ERBB2 signaling pathway.