ADRB2 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: P07550
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-03 (PR 1339)
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: ADRB2 encodes the beta-2 adrenergic receptor, a seven-transmembrane catecholamine GPCR that acts mainly at the plasma membrane. Epinephrine and norepinephrine binding activate bifurcated G protein signaling, especially Gs/cAMP/PKA and context-dependent Gi branches, with downstream effects on MAPK signaling, smooth-muscle and cardiovascular physiology, thermogenesis, and adipocyte lipolysis. Activated receptors are regulated by arrestin- and ubiquitin-dependent endocytosis, recycling, lysosomal sorting, and Golgi-associated palmitoylation-dependent trafficking. Beyond terminating signaling, internalized beta-arrestin-bound receptors can sustain G protein signaling from endosomes, so receptor output is shaped by subcellular location as well as ligand.
- Existing/core annotation action counts: ACCEPT: 56; KEEP_AS_NON_CORE: 38; MARK_AS_OVER_ANNOTATED: 26; MODIFY: 9
PN Consistency Summary
- Consistency: CONTRADICTION (PN projection rejected by review). PN node label itself says "Upstream lipophagy signaling," yet the type-node projects direct GO:0061724 lipophagy. The review, notes, and Falcon deep research all agree ADRB2 is the beta-2 adrenergic GPCR acting as an upstream signal for adipocyte lipophagy; the direct lipid-droplet/autolysosome machinery in the source paper is RAB7, not ADRB2 (PMID:23708524). The review keeps existing GO:1904504 positive regulation of lipophagy (IDA, in GOA) and declines direct lipophagy.
- PN story / NEW pressure: PN pressures a direct-process term (GO:0061724, OLS-verified real) onto an upstream signaling gene. The regulatory role is already captured in GOA (GO:1904504 positive regulation of lipophagy + GO:1905168 positive regulation of autophagosome maturation, both KEEP_AS_NON_CORE). No NEW direct term is defensible; the core function is GPCR/catecholamine signaling. Conclusion: PN over-reaches (regulation→direct process upgrade); already captured at the regulation level.
- Evidence alignment: PN reference (the tandfonline RAB7/autolysosomal-lipid-degradation article = PMID:23708524) is the same paper the review uses — and that paper's own data assign the direct machinery to RAB7, supporting the review's downgrade. No citation divergence; interpretation diverges (direct vs upstream).
- Verdict: PN direct-lipophagy projection over-reaches; review correctly retains positive-regulation-of-lipophagy and declines GO:0061724 (RAB7 is the direct factor). Recommended edits: [MAP] Keep ADRB2 mapping at GO:1904504 positive regulation of lipophagy; do not propagate direct GO:0061724 lipophagy.
Full Consistency Review
- UniProt: P07550 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
- PN placement:
Autophagy-Lysosome Pathway|Autophagy substrate selection|Marking substrates for selective autophagy|Lipophagy|Upstream lipophagy signaling ; PN-node mapping: type Lipophagy=mapped→GO:0061724 lipophagy (scope=ok_for_propagation; goa_status=supported_by_goa_regulation); group/class/branch=no_mapping; subtype Upstream lipophagy signaling=no_mapping.
- Consistency: CONTRADICTION (PN projection rejected by review). PN node label itself says "Upstream lipophagy signaling," yet the type-node projects direct GO:0061724 lipophagy. The review, notes, and Falcon deep research all agree ADRB2 is the beta-2 adrenergic GPCR acting as an upstream signal for adipocyte lipophagy; the direct lipid-droplet/autolysosome machinery in the source paper is RAB7, not ADRB2 (PMID:23708524). The review keeps existing GO:1904504 positive regulation of lipophagy (IDA, in GOA) and declines direct lipophagy.
- PN story / NEW pressure: PN pressures a direct-process term (GO:0061724, OLS-verified real) onto an upstream signaling gene. The regulatory role is already captured in GOA (GO:1904504 positive regulation of lipophagy + GO:1905168 positive regulation of autophagosome maturation, both KEEP_AS_NON_CORE). No NEW direct term is defensible; the core function is GPCR/catecholamine signaling. Conclusion: PN over-reaches (regulation→direct process upgrade); already captured at the regulation level.
- Mapping strategy: Direct precedent of TOMM20/HSPA8/RAB7A rejected as broader/mis-leveled. Here the PN-projected GO:0061724 is mis-leveled in the opposite direction — it asserts the direct process for a gene that only regulates it upstream. GO:0061724 should not propagate to ADRB2; the safe target is the regulation term already in GOA. The review even flags this as an open question (line ~2522: "Should PN projection for ADRB2 remain at GO:1904504 ... rather than direct GO:0061724").
- Evidence alignment: PN reference (the tandfonline RAB7/autolysosomal-lipid-degradation article = PMID:23708524) is the same paper the review uses — and that paper's own data assign the direct machinery to RAB7, supporting the review's downgrade. No citation divergence; interpretation diverges (direct vs upstream).
- Verdict: PN direct-lipophagy projection over-reaches; review correctly retains positive-regulation-of-lipophagy and declines GO:0061724 (RAB7 is the direct factor). Recommended edits: [MAP] Keep ADRB2 mapping at GO:1904504 positive regulation of lipophagy; do not propagate direct GO:0061724 lipophagy.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-03
- review_yaml: genes/human/ADRB2/ADRB2-ai-review.yaml
- PN workbook rows: 1
PN row 1: Autophagy-Lysosome Pathway | Autophagy substrate selection | Marking substrates for selective autophagy | Lipophagy | Upstream lipophagy signaling
- UniProt: P07550
- In branches: ALP
- Notes: Mediates beta-adrenergic receptor-stimulated lipophagy which decreases following inhibition of autophagy
- PN references (titles):
- Full article: β-adrenergic receptor-stimulated lipolysis requires the RAB7-mediated autolysosomal lipid degradation (tandfonline.com)
- PN-node mapping records (path + ancestors):
- [subtype] Autophagy-Lysosome Pathway|Autophagy substrate selection|Marking substrates for selective autophagy|Lipophagy|Upstream lipophagy signaling
status=no_mapping scope= GO=[]
rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Marking substrates for selective autophagy|Lipophagy
status=mapped scope=ok_for_propagation_to_go GO=[GO:0061724 lipophagy]
rationale: This PN type denotes factors that mark lipid cargo for selective autophagy. The category is narrower than the full lipophagy process, so propagation scope is the correct fit.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Marking substrates for selective autophagy
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
Projected GO annotations (1)
- GO:0061724 lipophagy | scope=ok_for_propagation_to_go | goa_status=supported_by_goa_regulation | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Marking substrates for selective autophagy|Lipophagy
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.