ABTB1 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q969K4
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-03 (PR 1328)
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: ABTB1 is a cytoplasmic ankyrin-repeat and BTB/POZ-domain protein with multiple splice isoforms. It was originally described as BPOZ/elongation factor 1A-binding protein and as a PTEN-responsive growth-suppressive factor in cancer cell assays. Its domain architecture and interaction with CUL3 support membership in a cullin-associated ubiquitin ligase complex, most plausibly a CRL3 context, but specific physiological substrates and direct ubiquitin-ligase substrate-adaptor activity remain poorly characterized.
- Existing/core annotation action counts: ACCEPT: 4; MARK_AS_OVER_ANNOTATED: 7; MODIFY: 2
PN Consistency Summary
- Consistency: Consistent in evidence, divergent in conclusion (deliberately). Deep research/notes: ABTB1 = cytoplasmic ankyrin+BTB/POZ protein, CUL3 interactor (UniProt NbExp=5), BPOZ/PTEN-responsive growth suppressor; no validated CRL3 substrate. The review accepts cytoplasm/cytosol, MODIFIES generic ligase-complex→GO:0031463 Cul3-RING ubiquitin ligase complex and protein binding→GO:0097602 cullin family protein binding, and declines the PN-projected GO:1990756 substrate-adaptor activity because no substrate-bridging assay exists. PN (substrate-receptor activity) vs review (CUL3 binding + CRL3 membership, no adaptor activity) is an evidence-based divergence, not a contradiction — the review is the more conservative, better-justified position.
- PN story / NEW pressure: PN asserts substrate-adaptor (receptor) activity via GO:1990756 (verified real; def. "usually mediated by F-box/BTB/POZ proteins"). Architecturally plausible but unproven for ABTB1 (no substrate). The review instead adds two verified, better-supported terms — GO:0031463 (Cul3-RING ubiquitin ligase complex; verified real) and GO:0097602 (cullin family protein binding; verified real) — as proposed replacements. Conclusion: PN's adaptor-activity claim over-reaches; the defensible additions are GO:0031463/GO:0097602, already captured in the review as MODIFY replacements.
- Evidence alignment: PN reference titles: PMID:15071497/rev and PMID:23912815/rev (Cul3/BTB substrate-receptor reviews). The review instead anchors CUL3 evidence on PMID:21145461 (CRL-network proteomics) + UniProt IntAct (CUL3 NbExp=5); the two PN review-PMIDs are not in the review reference list. Mild divergence (different supporting reviews) but same CRL3 biology.
- Verdict: Consistent; PN substrate-adaptor activity correctly held back (no substrate), review adds verified CRL3 complex + cullin-binding terms. Recommended edits: [MAP] Keep GO:1990756 non-propagating for ABTB1 pending substrate evidence (review's GO:0031463/GO:0097602 are the correct landing terms). Optional [REF]: consider adding PMID:15071497 / PMID:23912815 (PN-cited Cul3 reviews) to the review references for completeness.
Full Consistency Review
- UniProt: Q969K4 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
- PN placement:
UPS|E3 ubiquitin and UBL ligases|Cul3 substrate receptor|BTB-BACK|ankyrin ; PN-node mapping: subtype/type (BTB-BACK,ankyrin)=no_mapping; group Cul3 substrate receptor=mapped→GO:1990756 ubiquitin-like ligase-substrate adaptor activity (new_to_goa); class E3...ligases=context_only (GO:0061630 too_broad); branch UPS=no_mapping.
- Consistency: Consistent in evidence, divergent in conclusion (deliberately). Deep research/notes: ABTB1 = cytoplasmic ankyrin+BTB/POZ protein, CUL3 interactor (UniProt NbExp=5), BPOZ/PTEN-responsive growth suppressor; no validated CRL3 substrate. The review accepts cytoplasm/cytosol, MODIFIES generic ligase-complex→GO:0031463 Cul3-RING ubiquitin ligase complex and protein binding→GO:0097602 cullin family protein binding, and declines the PN-projected GO:1990756 substrate-adaptor activity because no substrate-bridging assay exists. PN (substrate-receptor activity) vs review (CUL3 binding + CRL3 membership, no adaptor activity) is an evidence-based divergence, not a contradiction — the review is the more conservative, better-justified position.
- PN story / NEW pressure: PN asserts substrate-adaptor (receptor) activity via GO:1990756 (verified real; def. "usually mediated by F-box/BTB/POZ proteins"). Architecturally plausible but unproven for ABTB1 (no substrate). The review instead adds two verified, better-supported terms — GO:0031463 (Cul3-RING ubiquitin ligase complex; verified real) and GO:0097602 (cullin family protein binding; verified real) — as proposed replacements. Conclusion: PN's adaptor-activity claim over-reaches; the defensible additions are GO:0031463/GO:0097602, already captured in the review as MODIFY replacements.
- Mapping strategy: Group node
Cul3 substrate receptor→GO:1990756 should be treated as non-propagating for ABTB1 until a substrate-bridging assay exists; the review's CRL3-complex membership (GO:0031463) is the appropriate landing point instead. Class-node GO:0061630 correctly context_only. The PN MF projection is broader/stronger than evidence supports — analogous to the rejected-projection precedent.
- Evidence alignment: PN reference titles: PMID:15071497/rev and PMID:23912815/rev (Cul3/BTB substrate-receptor reviews). The review instead anchors CUL3 evidence on PMID:21145461 (CRL-network proteomics) + UniProt IntAct (CUL3 NbExp=5); the two PN review-PMIDs are not in the review reference list. Mild divergence (different supporting reviews) but same CRL3 biology.
- Verdict: Consistent; PN substrate-adaptor activity correctly held back (no substrate), review adds verified CRL3 complex + cullin-binding terms. Recommended edits: [MAP] Keep GO:1990756 non-propagating for ABTB1 pending substrate evidence (review's GO:0031463/GO:0097602 are the correct landing terms). Optional [REF]: consider adding PMID:15071497 / PMID:23912815 (PN-cited Cul3 reviews) to the review references for completeness.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-03
- review_yaml: genes/human/ABTB1/ABTB1-ai-review.yaml
- PN workbook rows: 1
PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul3 substrate receptor | BTB-BACK | ankyrin
- UniProt: Q969K4
- In branches: UPS
- Signature domains: IPR000210, cd18497
- 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|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
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.