MIB1 (human, Q86YT6) review notes

Identity

• E3 ubiquitin-protein ligase MIB1 (EC 2.3.2.27). PANTHER PTHR24202 (official name "E3 UBIQUITIN-PROTEIN LIGASE MIB2") / PTHR24202:SF53 (E3 UBIQUITIN-PROTEIN LIGASE MIB1).
• IBA nodes: ubiquitin protein ligase activity, protein ubiquitination, cytoplasm PTN001197468; Notch signaling pathway and endocytosis PTN008608909.

Key findings

• MZM and REP domains bind JAG1 N-box and C-box; both needed for efficient ubiquitination and signaling; human MIB1 rescues fly mib1 PMID:25747658.
• "The dominant E3 ligase responsible for ligand ubiquitination in mammals is Mib1" PMID:25747658.
• Non-Notch substrates: SMN PMID:23615451, GABARAP PMID:28712572, TBK1 K63 PMID:21903422, PCM1/AZI1/CEP131 at centriolar satellites PMID:24121310.

Decisions

• Core: GO:0061630 in GO:0016567, GO:0007219, GO:0006897; cytoplasm/plasma membrane.
• All protein-binding rows REMOVE (partners are substrates; interaction not disputed).
• Considered NEW GO:0045747 positive regulation of Notch; comparator check (QuickGO): mouse Mib1 carries GO:0007219 IMP but not GO:0045747; human MIB2 has neither -> did not add.

Variant-relevant biology

• In mammals MIB1 is the main ligand E3; Neuralized (NEURL1/1B) is minor, in contrast to Drosophila where Neur is critical in neurogenesis.

Deep research

• Falcon deep research completed: file:human/MIB1/MIB1-deep-research-falcon.md (first attempt timed out at the 600 s wrapper default; rerun with --timeout 2700). Key statements quoted in the review are verbatim from that file.