DLL1

DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [provided by RefSeq]

delta-like 1 (Drosophila)

Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner (PubMed:11006133).

Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) (By similarity).

Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation (PubMed:11581320).

Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner. During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries. During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis. Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell. Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B-cells (By similarity).

Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor (PubMed:11581320).

Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression. Also plays a role during pancreatic cell development. During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression. Controls sprouting angiogenesis and subsequent vertical branch formation througth regulation on tip cell differentiation. Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. Plays a role during inner ear development; negatively regulates auditory hair cell differentiation. Plays a role during nephron development through Notch signaling pathway. Regulates growth, blood pressure and energy homeostasis (By similarity).

Astrocyte development Source: UniProtKB
Cell differentiation Source: UniProtKB
Cell fate determination Source: UniProtKB
Cerebellar molecular layer formation Source: UniProtKB
Cerebellar Purkinje cell layer structural organization Source: UniProtKB
Clathrin-dependent endocytosis Source: UniProtKB
Compartment pattern specification Source: Ensembl
Determination of left/right symmetry Source: BHF-UCL
Endothelial tip cell fate specification Source: UniProtKB
Energy homeostasis Source: UniProtKB
Heart looping Source: BHF-UCL
Hemopoiesis Source: UniProtKB
Inner ear development Source: Ensembl
Lateral inhibition Source: UniProtKB
Left/right axis specification Source: Ensembl
Loop of Henle development Source: Ensembl
Marginal zone B cell differentiation Source: UniProtKB
Negative regulation of cardiac muscle cell differentiation Source: Ensembl
Negative regulation of cell differentiation Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of epidermal cell differentiation Source: UniProtKB
Negative regulation of epithelial cell differentiation Source: UniProtKB
Negative regulation of glial cell apoptotic process Source: UniProtKB
Negative regulation of inner ear auditory receptor cell differentiation Source: Ensembl
Negative regulation of interleukin-10 production Source: UniProtKB
Negative regulation of myeloid cell differentiation Source: Ensembl
Negative regulation of myoblast differentiation Source: UniProtKB
Negative regulation of neuron differentiation Source: UniProtKB
Negative regulation of Notch signaling pathway Source: GO_Central
Nephron development Source: UniProtKB
Neuronal stem cell population maintenance Source: UniProtKB
Neuron fate specification Source: UniProtKB
Notch signaling pathway Source: UniProtKB
Notch signaling pathway involved in arterial endothelial cell fate commitment Source: UniProtKB
Organ growth Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of endocytosis Source: UniProtKB
Positive regulation of gene expression Source: Ensembl
Positive regulation of Notch signaling pathway Source: UniProtKB
Positive regulation of skeletal muscle tissue growth Source: UniProtKB
Positive regulation of sprouting angiogenesis Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Proximal/distal pattern formation Source: UniProtKB
Proximal tubule development Source: Ensembl
Regulation of blood pressure Source: UniProtKB
Regulation of cell adhesion Source: UniProtKB
Regulation of cell division Source: UniProtKB
Regulation of growth Source: UniProtKB
Regulation of neurogenesis Source: UniProtKB
Regulation of skeletal muscle tissue growth Source: UniProtKB
Regulation of somitogenesis Source: UniProtKB
Regulation of vascular endothelial growth factor signaling pathway Source: UniProtKB
Retina development in camera-type eye Source: UniProtKB
Retina morphogenesis in camera-type eye Source: UniProtKB
Skeletal muscle tissue growth Source: UniProtKB
Skin epidermis development Source: UniProtKB
Somite specification Source: Ensembl
Somitogenesis Source: UniProtKB
Spinal cord development Source: UniProtKB
Type B pancreatic cell development Source: UniProtKB

Apical cell membrane; Adherens junction; Membrane raft. Distributed around adherens junction in the apical endfeet through interactions with MAGI1.

Neurodevelopmental disorder with non-specific brain abnormalities and with or without seizures (NEDBAS):
An autosomal dominant disorder characterized by developmental delay, intellectual disability, seizures, autism spectrum disorder, behavioral abnormalities, and variable non-specific brain malformations.

Extracellular: 18-545
Helical: 546-568
Cytoplasmic: 569-723

Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation (By similarity). Ubiquitinated; promotes recycling back to the plasma membrane and confers a strong affinity for NOTCH1. Multi-ubiquitination of LYS-613 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling. Ubiquitinated by NEURL1B (By similarity).
Phosphorylated in a membrane association-dependent manner. Phosphorylation at Ser-697 requires the presence of Ser-694, whereas phosphorylation at Ser-694 occurs independently of the other site. Phosphorylation is required for full ligand activity in vitro and affects surface presentation, ectodomain shedding, and endocytosis.
O-fucosylated. Can be elongated to a disaccharide by MFNG.