DLL1 (human, O00548) review notes
Identity
- Delta-like protein 1; DSL-family transmembrane Notch ligand. PANTHER PTHR24049 / PTHR24049:SF38.
- IBA nodes: Notch binding PTN002371879; plasma membrane, Notch signaling pathway, negative regulation of Notch signaling PTN001170801.
Key findings (with provenance)
- Direct Ca2+-dependent binding to NOTCH1/NOTCH3 ectodomains PMID:11006133
- MNNL-EGF3 sufficient for NOTCH1 activation; NOTCH1 prefers DLL4 over DLL1 by >10-fold affinity PMID:23839946
- Soluble DLL1 is a weak activator; ICD needed for full NOTCH2 S3 cleavage PMID:11823422
- C-terminal ATEV PDZ-binding motif binds MAGI1-3 PDZ4 PMID:15509766; SYNJ2BP stabilises DLL1/DLL4 via PDZ motif PMID:24025447.
- Cis-inhibition: NOTCH2NL relieves cis DLL1-NOTCH interactions PMID:29856955
- Lymphoid fate: DLL1 blocks B and promotes T/NK precursors PMID:11581320.
- DOS motif present in EGF1-2 (unlike DLL4) [file:human/DLL1/DLL1-deep-research-falcon.md].
- Ubiquitinated by MIB1 (Lys-613) -> endocytosis/pulling force (UniProt, by similarity).
Curation decisions
- Core: Notch binding (GO:0005112), receptor ligand activity (GO:0048018), PDZ domain binding (GO:0030165, via MODIFY of protein binding/Tat binding rows); Notch signaling pathway, lateral inhibition; plasma membrane.
- Tat protein binding (GO:0030957, IPI PMID:15509766) -> MODIFY to PDZ domain binding (partners are MAGIs).
- Many mouse-orthology developmental terms kept as non-core; blood pressure/energy homeostasis/growth/proliferation/transcription/endocytosis terms marked over-annotated.
Variant-relevant biology
- DLL1 has a DOS motif (DLL4 does not); has C-terminal PDZ-binding ATEV motif (shared with DLL4, absent from JAG1); acts in trans (activation) and cis (inhibition).
Deep research
- Falcon deep research completed: file:human/DLL1/DLL1-deep-research-falcon.md (the wrapper reported a 600 s timeout, but the client finished writing the report after 941 s). Key statements quoted in the review are verbatim from that file.