Dll1 (mouse) review notes
UniProt Q61483 (DLL1_MOUSE), Delta-like protein 1, 722 aa, type I transmembrane DSL ligand.
PANTHER PTHR24049 (CRUMBS FAMILY MEMBER) per UniProt DR line. MGI:104659.
Notch-module role: canonical activating Delta-class (DSL) Notch ligand (signal-sending cell).
Molecular function
- Binds Notch1/Notch2 in trans and activates cleavage and RBP-J-dependent transcription
PMID:10958687
PMID:10958687
- Fringe increases Delta1 binding and Notch1 activation PMID:15574878
- Ubiquitinated by E3 ligases Mib1 and Neurl1/Neurl1b; ubiquitination needed for recycling and Notch-binding
competence and to drive Notch1 transendocytosis
PMID:16000382
PMID:17003037
PMID:18676613
PMID:21985982
- Itself a substrate of regulated intramembrane proteolysis (ADAM10 shedding then gamma-secretase); ICD partly nuclear
PMID:12794186
- C-terminal PDZ-binding motif binds MAGI1/MAGI2 (Acvrinp1) PDZ domains; MAGI1 recruits Dll1 to adherens junctions
PMID:14529612
PMID:15908431
- MT1-MMP (MMP14) cleaves Dll1 on stromal cells to dampen Notch signalling PMID:21572390.
Localisation
Biological processes
- Lateral inhibition in neurogenesis, inner ear hair cells, intestinal secretory cells
PMID:16495313
PMID:18997111
- Somitogenesis (segmentation clock, somite polarity), left-right asymmetry via Nodal
PMID:12730124
- Arterial identity (DLL1 activates Notch1 in fetal arteries) PMID:19144989
- Marginal zone B cells, adult neural stem cell quiescence, satellite cells, epidermis: pleiotropic.
Pathway-variant relevance
- Canonical activating Delta with MNNL/C2, DSL (InterPro IPR001774) and eight EGF repeats. Falcon deep
research reports a DOS motif in the EGF1-2 region of Dll1 (absent from Dll4), citing Hirano et al. 2020
[file:mouse/Dll1/Dll1-deep-research-falcon.md "Dll1 also contains a Delta-and-OSM-11-like (DOS) motif within the EGF1–2 region, which is present in Dll1 but absent from Dll4"];
primary source not independently checked here. Requires Mib1 (and Neurl) ubiquitination to signal. Dll4 paralog partially redundant but
functionally divergent PMID:26114479. Dll3 is the divergent non-activating paralog.
Deep research
Falcon deep research completed (Dll1-deep-research-falcon.md; the wrapper reported a 600 s timeout but the
orphaned falcon client finished and wrote the file). Also notes cis-inhibition by Dll1
[file:mouse/Dll1/Dll1-deep-research-falcon.md "Dll1 also mediates cis-inhibition when present in the same cell as Notch"].
2026-10-12 Ortholog/family audit (Dll1, Dll3, Hes7, Rbpj)
- GOA refreshed (
just fetch-gene mouse Dll1): no new rows; every GOA row has a review entry and no stale entries remain.
- Compared with human DLL1, Drosophila Dl and sea urchin Delta reviews. Core MFs (Notch binding, receptor ligand activity), Notch signaling pathway, plasma membrane, lateral inhibition and the IBA cis-inhibition term (GO:0045746, KEEP_AS_NON_CORE) agree across all four.
- Changed: GO:0045747 positive regulation of Notch signaling pathway (9 rows) from ACCEPT to KEEP_AS_NON_CORE, matching human DLL1. The ligand is part of the Notch pathway itself (GO:0007219), so the regulation term is correct but not the core statement.
- Changed: GO:0030957 Tat protein binding (IEA and ISO rows, transferred from human O00548) from REMOVE to MODIFY, with GO:0030165 PDZ domain binding as the replacement. The human source IPI is a study of Delta binding to MAGI PDZ4 PMID:15509766. The human review already MODIFYs it the same way, so the earlier mouse reason (an HIV-1 Tat interaction) was wrong.
- Donor-side fix: human DLL1 GO:0005509 calcium ion binding changed from ACCEPT to KEEP_AS_NON_CORE. Its own reason already called it non-core, and mouse Dll1, fly Dl and sea urchin Delta all treat it that way.
- Family (Dll3): both genes receive identical IBAs from PTN001170801 and PTN002371879. The differences in treatment rest on evidence specific to Dll3 PMID:16144902: for Dll3, Notch signaling pathway is MODIFIED to negative regulation, plasma membrane is non-core, and cis-inhibition is core.
- Status set to COMPLETE.