Names & Taxonomy
- Uniprot ID:
- O00548
- Entry Name:
- DLL1_HUMAN
- Status:
- reviewed
- Protein Names:
- Delta-like protein 1 (Drosophila Delta homolog 1) (Delta1) (H-Delta-1)
- Gene Names:
- DLL1 UNQ146/PRO172
- Gene Names Orf:
- UNQ146/PRO172
- Gene Names Primary:
- DLL1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 723
- Sequence:
- MGSRCALALAVLSALLCQVWSSGVFELKLQEFVNKKGLLGNRNCCRGGAGPPPCACRTFFRVCLKHYQASVSPEPPCTYGSAVTPVLGVDSFSLPDGGGADSAFSNPIRFPFGFTWPGTFSLIIEALHTDSPDDLATENPERLISRLATQRHLTVGEEWSQDLHSSGRTDLKYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGERGEKVCNPGWKGPYCTEPICLPGCDEQHGFCDKPGECKCRVGWQGRYCDECIRYPGCLHGTCQQPWQCNCQEGWGGLFCNQDLNYCTHHKPCKNGATCTNTGQGSYTCSCRPGYTGATCELGIDECDPSPCKNGGSCTDLENSYSCTCPPGFYGKICELSAMTCADGPCFNGGRCSDSPDGGYSCRCPVGYSGFNCEKKIDYCSSSPCSNGAKCVDLGDAYLCRCQAGFSGRHCDDNVDDCASSPCANGGTCRDGVNDFSCTCPPGYTGRNCSAPVSRCEHAPCHNGATCHERGHRYVCECARGYGGPNCQFLLPELPPGPAVVDLTEKLEGQGGPFPWVAVCAGVILVLMLLLGCAAVVVCVRLRLQKHRPPADPCRGETETMNNLANCQREKDISVSIIGATQIKNTNKKADFHGDHSADKNGFKARYPAVDYNLVQDLKGDDTAVRDAHSKRDTKCQPQGSSGEEKGTPTTLRGGEASERKRPDSGCSTSKDTKYQSVYVISEEKDECVIATEV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Apical cell membrane
Function
- Function:
- 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).
- Gene Ontology Go:
- adherens junction
apical plasma membrane
cytoplasmic vesicle
extracellular region
integral component of plasma membrane
membrane raft
plasma membrane
calcium ion binding
Notch binding
Tat protein binding
astrocyte development
cell differentiation
cell fate determination
cerebellar molecular layer formation
cerebellar Purkinje cell layer structural organization
clathrin-mediated endocytosis
compartment pattern specification
determination of left/right symmetry
endothelial tip cell fate specification
heart looping
hemopoiesis
inner ear development
lateral inhibition
left/right axis specification
loop of Henle development
marginal zone B cell differentiation
negative regulation of auditory receptor cell differentiation
negative regulation of cell differentiation
negative regulation of cell proliferation
negative regulation of epidermal cell differentiation
negative regulation of epithelial cell differentiation
negative regulation of glial cell apoptotic process
negative regulation of interleukin-10 production
negative regulation of myeloid cell differentiation
negative regulation of myoblast differentiation
negative regulation of neuron differentiation
nephron development
neuron fate specification
neuronal stem cell population maintenance
Notch receptor processing
Notch signaling pathway
Notch signaling pathway involved in arterial endothelial cell fate commitment
organ growth
positive regulation of cell proliferation
positive regulation of endocytosis
positive regulation of Notch signaling pathway
positive regulation of skeletal muscle tissue growth
positive regulation of sprouting angiogenesis
positive regulation of transcription from RNA polymerase II promoter
proximal tubule development
proximal/distal pattern formation
regulation of blood pressure
regulation of cell adhesion
regulation of cell division
regulation of energy homeostasis
regulation of growth
regulation of neurogenesis
regulation of skeletal muscle tissue growth
regulation of somitogenesis
regulation of vascular endothelial growth factor signaling pathway
retina development in camera-type eye
retina morphogenesis in camera-type eye
skeletal muscle tissue growth
skin epidermis development
somite specification
somitogenesis
spinal cord development
type B pancreatic cell development - Gene Ontology Biological Process:
- astrocyte development
cell differentiation
cell fate determination
cerebellar molecular layer formation
cerebellar Purkinje cell layer structural organization
clathrin-mediated endocytosis
compartment pattern specification
determination of left/right symmetry
endothelial tip cell fate specification
heart looping
hemopoiesis
inner ear development
lateral inhibition
left/right axis specification
loop of Henle development
marginal zone B cell differentiation
negative regulation of auditory receptor cell differentiation
negative regulation of cell differentiation
negative regulation of cell proliferation
negative regulation of epidermal cell differentiation
negative regulation of epithelial cell differentiation
negative regulation of glial cell apoptotic process
negative regulation of interleukin-10 production
negative regulation of myeloid cell differentiation
negative regulation of myoblast differentiation
negative regulation of neuron differentiation
nephron development
neuronal stem cell population maintenance
neuron fate specification
Notch receptor processing
Notch signaling pathway
Notch signaling pathway involved in arterial endothelial cell fate commitment
organ growth
positive regulation of cell proliferation
positive regulation of endocytosis
positive regulation of Notch signaling pathway
positive regulation of skeletal muscle tissue growth
positive regulation of sprouting angiogenesis
positive regulation of transcription from RNA polymerase II promoter
proximal/distal pattern formation
proximal tubule development
regulation of blood pressure
regulation of cell adhesion
regulation of cell division
regulation of energy homeostasis
regulation of growth
regulation of neurogenesis
regulation of skeletal muscle tissue growth
regulation of somitogenesis
regulation of vascular endothelial growth factor signaling pathway
retina development in camera-type eye
retina morphogenesis in camera-type eye
skeletal muscle tissue growth
skin epidermis development
somite specification
somitogenesis
spinal cord development
type B pancreatic cell development - Gene Ontology Molecular Function:
- calcium ion binding
Notch binding
Tat protein binding - Gene Ontology Cellular Component:
- adherens junction
apical plasma membrane
cytoplasmic vesicle
extracellular region
integral component of plasma membrane
membrane raft
plasma membrane - Keywords:
- 3D-structure
Alternative splicing
Cell junction
Cell membrane
Complete proteome
Developmental protein
Differentiation
Disulfide bond
EGF-like domain
Glycoprotein
Isopeptide bond
Membrane
Notch signaling pathway
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Signal
Transmembrane
Transmembrane helix
Ubl conjugation