ABTB3

UniProt: A6QL63 (=BTBD11) · 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, transmembrane ; PN-node mapping: group Cul3 substrate receptor=mapped→GO:1990756 ubiquitin-like ligase-substrate adaptor activity (new_to_goa); class=context_only (too_broad→GO:0061630); subtype/type/branch=no_mapping.
Consistency: CONTRADICTION (PN projection rejected by review). The PN node projects the same Cul3-adaptor term (GO:1990756) as for paralog ABTB2, purely on BTB-BACK/ankyrin domain architecture. Deep research, notes, and review YAML all converge instead on a synaptic scaffold/stabilizer role: mouse ortholog Btbd11 binds PSD-95 via a C-terminal PDZ-binding motif, stabilizes PSD-95, and supports glutamatergic input onto PV interneurons (PMID:37261953). The review explicitly declines GO:1990756: "the available ABTB3/Btbd11 evidence does not show CUL3 binding, CRL3 complex membership, a ubiquitinated substrate, or substrate-adaptor activity."
PN story / NEW pressure: PN asserts ubiquitin-ligase adaptor activity with no gene-level support for this gene — a domain-architecture inference. The actual GO captures the real biology (GO:0030165 PDZ domain binding ACCEPT; GO:0098978 glutamatergic synapse ACCEPT) and the review adds orthology-supported NEW terms GO:0050821 protein stabilization and GO:0035249 synaptic transmission, glutamatergic. The Cul3-adaptor story over-reaches and is correctly not added.
Mapping strategy: This gene shows the Cul3-substrate-receptor group mapping does not safely propagate to all BTB-BACK-ankyrin members. GO:1990756 should be suppressed for ABTB3 pending direct CUL3/CRL3 evidence — a per-gene exception within an otherwise valid group mapping (contrast ABTB2, where it is supported). Precedent: reject a projected term lacking gene-level support.
Evidence alignment: PN row references (PMID:15071497, 23912815 — generic Cul3/BTB reviews) do not overlap the review's primary evidence (PMID:37261953, the Btbd11 synaptic study). Complete divergence in evidence base, reflecting the domain-only vs functional-evidence split.
Verdict: PN Cul3-adaptor projection over-reaches (domain-only, contradicted by synaptic-function evidence); review correctly rejects GO:1990756. Recommended edits: [MAP] Suppress GO:1990756 projection for ABTB3 (no CUL3/CRL3/substrate evidence); retain the group mapping for genes with direct support (e.g. ABTB2).