ERBB2 signaling pathway module

ERBB2/HER2 acts as a ligandless preferred dimerization partner for ERBB receptors, especially ERBB3 after neuregulin binding, producing potent PI3K-AKT and MAPK output.

MODULE:erbb2_signalingDRAFTSignaling Pathwaymodules/erbb2_signaling.yaml
ERBB2 signaling pathwayGO:0038128
file:modules/erbb2_signaling-deep-research-falcon.md
ERBB2 signaling pathway Falcon module review
Falcon/Edison module review generated 2026-06-28 is linked as supporting evidence for module boundaries, core mechanism, variation, constraints, and failure modes; open questions in that report require manual review before promotion to curated knowledge gaps.
GO:0038128
ERBB2 signaling pathway
The module is grounded in the GO biological process term for ERBB2 signaling pathway.
PANTHER:PTN001230349
PAINT node PTN001230349 for ERBB3
Local PAINT node in PTHR24416. Carries four positive IBD rows and no loss rows of its own: C:GO:0005886, C:GO:0043235, F:GO:0004714, P:GO:0007169. Descendant nodes cite it as their with-source when recording a loss, so the kinase activity is ancestral here and struck out further down. PAINT date 20260529.
PANTHER:PTN002814617
PAINT node PTN002814617 for ERBB3
Local PAINT node in PTHR24416, the ERBB3 lineage. Records F:GO:0004714 as LOST (IRD) and carries positive IBD F:GO:0038131 (neuregulin receptor activity) and F:GO:0038132. The loss is confined to the receptor tyrosine kinase activity; P:GO:0007169 is not struck out on this lineage. PAINT date 20200401.
PANTHER:PTN000698827
PAINT node PTN000698827 for ERBB2
Local PAINT IBD node in PTHR24416 with propagated terms C:GO:0009925, P:GO:0007173, P:GO:0043410, P:GO:0050679; PAINT date 20250904.
PANTHER:PTN008302071
PAINT node PTN008302071 for PIK3R1
Local PAINT IBD node in PTHR10155 with propagated terms C:GO:0005943; PAINT date 20240516.
PANTHER:PTN005273574
PAINT node PTN005273574 for GRB2
Local PAINT IBD node in PTHR46037 with propagated terms C:GO:0005737, C:GO:0005886, C:GO:0008180, F:GO:0001784, F:GO:0005154, P:GO:0007165; PAINT date 20260530.

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.

4Nodes
3Parts
0Variant Sets
0Variants
5Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • erbb2_signaling-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (2/5 grounded genes reviewed)

1 complete review(s) · 2 with deep research · 3 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
GRB2 P62993 ✓ 948/949 ✓
ERBB2 P04626 ✗ — —
ERBB3 P21860 ✗ — —
PIK3R1 P27986 ✓ ✓ ✓
NRG1 Q02297 ✗ — —

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
ERBB2 signaling pathwaySignaling Pathwayerbb2_signaling
ERBB2 signaling pathwayGO:0038128
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes erbb2 kinase activation.
ERBB2 kinase activation leads to pi3k and mapk output.
Part 1: neuregulin-erbb3 input
Neuregulin-ERBB3 inputRegulatory Stepneuregulin_erbb3_input

Neuregulin binding to ERBB3 promotes ERBB2-containing receptor dimers.

Annotons

NRG1 ligand
nrg1_nrg1_ligand
Participant: Gene Product: NRG1
Gene Product:
NRG1UniProtKB:Q02297

Function

signaling receptor bindingGO:0005102

Curated exemplar for the nrg1 ligand role in ERBB2 signaling pathway.

ERBB3 co-receptor
erbb3_erbb3_co_receptor
Participant: Family: ERBB3 co-receptor family/ortholog group
Family:
ERBB3 co-receptor family/ortholog groupPANTHER:PTHR24416
Representative Members: ERBB3UniProtKB:P21860

Function

neuregulin receptor activity (catalytically dead co-receptor)GO:0038131

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).

Part 2: erbb2 kinase activation
ERBB2 kinase activationReactionerbb2_kinase_activation

ERBB2 supplies the strong kinase-active partner in the receptor dimer.

Annotons

ERBB2 receptor kinase
erbb2_erbb2_receptor_kinase
Participant: Family: ERBB2 receptor kinase family/ortholog group
Family:
ERBB2 receptor kinase family/ortholog groupPANTHER:PTHR24416
Representative Members: ERBB2UniProtKB:P04626

Function

transmembrane receptor protein tyrosine kinase activityGO:0004714

Curated exemplar for the erbb2 receptor kinase role in ERBB2 signaling pathway.

Part 3: pi3k and mapk output
PI3K and MAPK outputRegulatory Steperbb2_pi3k_mapk_output

ERBB2/ERBB3 phosphotyrosines recruit PI3K and adaptor proteins to drive growth and survival.

Annotons

PIK3R1 p85 adaptor
pik3r1_pik3r1_p85_adaptor
Participant: Family: PIK3R1 p85 adaptor family/ortholog group
Family:
PIK3R1 p85 adaptor family/ortholog groupPANTHER:PTHR10155
Representative Members: PIK3R1UniProtKB:P27986

Curated exemplar for the pik3r1 p85 adaptor role in ERBB2 signaling pathway.

GRB2 adaptor
grb2_grb2_adaptor
Participant: Family: GRB2 adaptor family/ortholog group
Family:
GRB2 adaptor family/ortholog groupPANTHER:PTHR46037
Representative Members: GRB2UniProtKB:P62993

Curated exemplar for the grb2 adaptor role in ERBB2 signaling pathway.