JAG1 (human, P78504) review notes
Identity
- Protein jagged-1; Serrate-class DSL ligand. PANTHER PTHR12916 ("CYTOCHROME C OXIDASE POLYPEPTIDE VIC-2", official name) / PTHR12916:SF12 (DELTA-LIKE PROTEIN).
- IBA: Notch binding from PTN002371879.
Key findings
- Binds NOTCH1/NOTCH3 directly, Ca2+-dependent PMID:11006133.
- DSL-EGF3 crystal structure; same DSL face for cis and trans interactions PMID:18660822.
- MIB1 recognises two epitopes (N-box, C-box) in the JAG1 tail PMID:25747658.
- JAG1 is a ligand for CD46 on T cells PMID:23086448
- Alagille syndrome by haploinsufficiency PMID:9207787; TOF/PS variants lose Notch activation PMID:20437614; CMT2HH variants impair glycosylation/surface expression PMID:32065591.
- Soluble JAG1 ectodomain antagonises endogenous JAG1 signaling PMID:11427524 -> adhesion/migration phenotypes from sJ1 (PMID:11549580) treated as over-annotation.
- LFNG/MFNG reduce JAG1-triggered NOTCH2 signaling PMID:11346656.
- HTRA1 cleaves JAG1 ICD PMID:29713059.
Decisions
- Core: Notch binding; receptor ligand activity (NEW, IMP PMID:20437614; comparator DLL1 carries GO:0048018 IDA).
- growth factor activity -> MODIFY to receptor ligand activity; structural molecule activity -> REMOVE.
- protein binding rows: NOTCH1 -> Notch binding; CD46 -> signaling receptor binding; PDZ survey -> PDZ domain binding; HTRA1/VASN -> REMOVE.
Variant-relevant biology
- Serrate-type ligand: 16 EGF repeats + cysteine-rich region; Fringe-sensitive (Fringe reduces Jagged signaling through NOTCH1/2); C-terminal PDZ motif; JAG1-CD46 non-Notch receptor interaction.
Deep research
- Falcon deep research completed: file:human/JAG1/JAG1-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.
- Deep research: JAG1 cis-inhibition is receptor-dependent (weak on NOTCH1, stronger on NOTCH2); N-terminal region is a C2-type phospholipid-binding domain [file:human/JAG1/JAG1-deep-research-falcon.md].