Glucocorticoid receptor signaling pathway module

Glucocorticoid receptor signaling couples steroid ligand binding, HSP90/co-chaperone regulation, nuclear translocation, and co-regulator exchange to anti-inflammatory and metabolic transcriptional programs.

MODULE:glucocorticoid_receptor_signalingDRAFTSignaling Pathwaymodules/glucocorticoid_receptor_signaling.yaml
nuclear receptor-mediated glucocorticoid signaling pathwayGO:0042921
file:modules/glucocorticoid_receptor_signaling-deep-research-falcon.md
Glucocorticoid receptor 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:0042921
nuclear receptor-mediated glucocorticoid signaling pathway
The module is grounded in the GO biological process term for nuclear receptor-mediated glucocorticoid signaling pathway.
PANTHER:PTN000163527
PAINT node PTN000163527 for HSP90AA1
Local PAINT IBD node in PTHR11528 with propagated terms F:GO:0005524, F:GO:0016887; PAINT date 20260528.
PANTHER:PTN000163629
PAINT node PTN000163629 for HSP90AA1
Local PAINT IBD node in PTHR11528 with propagated terms C:GO:0005829, C:GO:0005886, C:GO:0032991, P:GO:0050821; PAINT date 20260528.
PANTHER:PTN002471265
PAINT node PTN002471265 for FKBP5
Local PAINT IBD node in PTHR10516 with propagated terms F:GO:0003755, P:GO:0006457; PAINT date 20250902.

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; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. 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
8Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • glucocorticoid_receptor_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 (1/6 grounded genes reviewed)

1 complete review(s) · 0 with deep research · 5 missing review · 1 reviewed but lacking deep research

Gene Review Complete Deep research
FKBP5 Q13451 ✓ ✓ ✗
NCOR1 O75376 ✗ — —
NR3C1 P04150 ✗ — —
HSP90AA1 P07900 ✗ — —
NCOA2 Q15596 ✗ — —
NCOA1 Q15788 ✗ — —

Details

Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634
Glucocorticoid receptor signaling pathwaySignaling Pathwayglucocorticoid_receptor_signaling
nuclear receptor-mediated glucocorticoid signaling pathwayGO:0042921
Context
metazoaNCBITaxon:33208
plasma membraneGO:0005886 cytosolGO:0005829 nucleusGO:0005634

Connections

The initiating event promotes glucocorticoid receptor activation.
Glucocorticoid receptor activation leads to glucocorticoid transcriptional output.
Part 1: glucocorticoid receptor chaperone cycle
Glucocorticoid receptor chaperone cycleRegulatory Stepglucocorticoid_receptor_chaperone_cycle

HSP90AA1 and FKBP5 maintain ligand-responsive glucocorticoid receptor complexes.

Annotons

HSP90 chaperone
hsp90aa1_hsp90_chaperone
Participant: Family: HSP90 chaperone family/ortholog group
Family:
HSP90 chaperone family/ortholog groupPANTHER:PTHR11528
Representative Members: HSP90AA1UniProtKB:P07900

Curated exemplar for the hsp90 chaperone role in nuclear receptor-mediated glucocorticoid signaling pathway.

FKBP5 co-chaperone
fkbp5_fkbp5_co_chaperone
Participant: Family: FKBP5 co-chaperone family/ortholog group
Family:
FKBP5 co-chaperone family/ortholog groupPANTHER:PTHR10516
Representative Members: FKBP5UniProtKB:Q13451

Curated exemplar for the fkbp5 co-chaperone role in nuclear receptor-mediated glucocorticoid signaling pathway.

Ligand-activated glucocorticoid receptor
nr3c1_ligand_activated_glucocorticoid_receptor
Participant: Gene Product: NR3C1
Gene Product:
NR3C1UniProtKB:P04150

Curated exemplar for the ligand-activated glucocorticoid receptor role in nuclear receptor-mediated glucocorticoid signaling pathway.

Part 2: glucocorticoid receptor activation
Glucocorticoid receptor activationRegulatory Stepglucocorticoid_receptor_activation

Ligand-bound NR3C1 translocates to the nucleus and binds regulatory DNA.

Annotons

Glucocorticoid receptor
nr3c1_glucocorticoid_receptor
Participant: Gene Product: NR3C1
Gene Product:
NR3C1UniProtKB:P04150

Curated exemplar for the glucocorticoid receptor role in nuclear receptor-mediated glucocorticoid signaling pathway.

Nuclear receptor coactivator 1
ncoa1_nuclear_receptor_coactivator_1
Participant: Gene Product: NCOA1
Gene Product:
NCOA1UniProtKB:Q15788

Curated exemplar for the nuclear receptor coactivator 1 role in nuclear receptor-mediated glucocorticoid signaling pathway.

Part 3: glucocorticoid transcriptional output
Glucocorticoid transcriptional outputRegulatory Stepglucocorticoid_transcriptional_output

NR3C1 recruits co-regulators to drive or repress glucocorticoid-responsive transcription.

Annotons

Nuclear receptor coactivator 2
ncoa2_nuclear_receptor_coactivator_2
Participant: Gene Product: NCOA2
Gene Product:
NCOA2UniProtKB:Q15596

Curated exemplar for the nuclear receptor coactivator 2 role in nuclear receptor-mediated glucocorticoid signaling pathway.

Nuclear receptor corepressor
ncor1_nuclear_receptor_corepressor
Participant: Gene Product: NCOR1
Gene Product:
NCOR1UniProtKB:O75376

Curated exemplar for the nuclear receptor corepressor role in nuclear receptor-mediated glucocorticoid signaling pathway.

NR3C1 transcriptional receptor
nr3c1_nr3c1_transcriptional_receptor
Participant: Gene Product: NR3C1
Gene Product:
NR3C1UniProtKB:P04150

Curated exemplar for the nr3c1 transcriptional receptor role in nuclear receptor-mediated glucocorticoid signaling pathway.