ABTB2 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q8N961
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-03 (PR 1331)
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: ABTB2 is a large ankyrin-repeat and BTB/POZ-domain protein with protein-protein interaction domains and isoform diversity. Direct experimental work in pancreatic ductal adenocarcinoma models supports a substrate-adaptor-like role in which ABTB2 binds TRAP1, promotes TRAP1 ubiquitination-dependent degradation, and suppresses Wnt/beta-catenin and PI3K/Akt signaling. ABTB2 has been detected in the nucleoplasm, but its normal tissue substrates and broader physiological roles remain incompletely defined.
- Existing/core annotation action counts: KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 2; NEW: 2
PN Consistency Summary
- Consistency: Deep-research (manual fallback), notes, review YAML, and the PN Cul3-adaptor mapping are mutually consistent. All converge on ABTB2 as a BTB/POZ substrate-adaptor that binds CUL3 and promotes TRAP1 ubiquitin-dependent degradation (PMID:41322190). No contradictions. The review prudently treats older BPOZ-2 papers as nomenclature-ambiguous with ABTB1 and excludes them as primary evidence.
- PN story / NEW pressure: PN asserts adaptor activity not in the original GOA (which had only GO:0046982 heterodimerization IEA, GO:0005515 protein binding IPI, GO:0005654 nucleoplasm). The review adds the PN-projected GO:1990756 (OLS-verified real) as a direct IDA NEW annotation, supported by ABTB2-TRAP1 co-IP, TRAP1 ubiquitination/degradation, and reported ABTB2-cullin-3 interaction, plus companion GO:0016567 protein ubiquitination. This is gene-specific support, not domain-only projection. Conclusion: legitimate ADD, executed in the review.
- Evidence alignment: PN row references (PMID:15071497, 23912815 — generic Cul3/BTB reviews) do NOT overlap the review's primary evidence (PMID:41322190, the 2025 PDAC study); the review rests on stronger gene-specific data than the PN row's domain-review citations. Generic 14-3-3 interactome (PMID:36931259) shared but marked over-annotated.
- Verdict: Fully consistent; PN GO:1990756 projection validated by direct evidence and correctly added as NEW. Recommended edits: none (mapping and review aligned).
Full Consistency Review
- UniProt: Q8N961 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
- PN placement:
Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK, variant|ankyrin ; PN-node mapping: group Cul3 substrate receptor=mapped→GO:1990756 ubiquitin-like ligase-substrate adaptor activity (new_to_goa); class E3 ubiquitin and UBL ligases=context_only (too_broad→GO:0061630); subtype/type/branch=no_mapping.
- Consistency: Deep-research (manual fallback), notes, review YAML, and the PN Cul3-adaptor mapping are mutually consistent. All converge on ABTB2 as a BTB/POZ substrate-adaptor that binds CUL3 and promotes TRAP1 ubiquitin-dependent degradation (PMID:41322190). No contradictions. The review prudently treats older BPOZ-2 papers as nomenclature-ambiguous with ABTB1 and excludes them as primary evidence.
- PN story / NEW pressure: PN asserts adaptor activity not in the original GOA (which had only GO:0046982 heterodimerization IEA, GO:0005515 protein binding IPI, GO:0005654 nucleoplasm). The review adds the PN-projected GO:1990756 (OLS-verified real) as a direct IDA NEW annotation, supported by ABTB2-TRAP1 co-IP, TRAP1 ubiquitination/degradation, and reported ABTB2-cullin-3 interaction, plus companion GO:0016567 protein ubiquitination. This is gene-specific support, not domain-only projection. Conclusion: legitimate ADD, executed in the review.
- Mapping strategy: This gene strengthens the Cul3-substrate-receptor group mapping with direct experimental evidence (unlike its paralog ABTB3). The group-level GO:1990756 scope is appropriate (adaptor activity, not catalytic E3); the review correctly avoids GO:0061630 ubiquitin protein ligase activity. No change needed.
- Evidence alignment: PN row references (PMID:15071497, 23912815 — generic Cul3/BTB reviews) do NOT overlap the review's primary evidence (PMID:41322190, the 2025 PDAC study); the review rests on stronger gene-specific data than the PN row's domain-review citations. Generic 14-3-3 interactome (PMID:36931259) shared but marked over-annotated.
- Verdict: Fully consistent; PN GO:1990756 projection validated by direct evidence and correctly added as NEW. Recommended edits: none (mapping and review aligned).
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-03
- review_yaml: genes/human/ABTB2/ABTB2-ai-review.yaml
- PN workbook rows: 1
PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul3 substrate receptor | BTB-BACK, variant | ankyrin
- UniProt: Q8N961
- In branches: UPS
- Signature domains: IPR000210, cd18526
- Auxiliary domains: IPR002110
- PN references (titles):
- 15071497 / rev
- 23912815 / rev
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK, variant|ankyrin
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK, variant
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor
status=mapped scope=ok_for_propagation_to_go GO=[GO:1990756 ubiquitin-like ligase-substrate adaptor activity]
rationale: This PN group captures substrate receptors/adaptors for cullin/UBL ligase systems. The shared GO molecular-function target is ubiquitin-like ligase-substrate adaptor activity.
- [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
- [branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
Projected GO annotations (1)
- GO:1990756 ubiquitin-like ligase-substrate adaptor activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul3 substrate receptor
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.