DLL1 [The Human Chemical-Genetic Interaction Map Project]

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======= DLL1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DLL1
  * **<color #00a2e8>Official Name</color>**: delta like canonical Notch ligand 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=28514|28514]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O00548|O00548]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DLL1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DLL1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606582|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:   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, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:P97677, ECO:0000250|UniProtKB:Q61483, ECO:0000269|PubMed:11006133, ECO:0000269|PubMed:11581320}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|EGF|
|DSL|
|MNNL|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cerebellar molecular layer formation|
|Notch signaling pathway involved in arterial endothelial cell fate commitment|
|lateral inhibition|
|cerebellar molecular layer morphogenesis|
|cell-cell signaling involved in cell fate commitment|
|cerebellar Purkinje cell layer structural organization|
|endothelial tip cell fate specification|
|cerebellar molecular layer development|
|arterial endothelial cell fate commitment|
|cerebellar cortex structural organization|
|skeletal muscle tissue growth|
|blood vessel endothelial cell fate specification|
|positive regulation of skeletal muscle tissue growth|
|blood vessel endothelial cell fate commitment|
|endothelial cell fate specification|
|negative regulation of mechanoreceptor differentiation|
|negative regulation of inner ear receptor cell differentiation|
|negative regulation of inner ear auditory receptor cell differentiation|
|proximal tubule development|
|compartment pattern specification|
|inhibition of neuroepithelial cell differentiation|
|regulation of skeletal muscle tissue growth|
|somite specification|
|arterial endothelial cell differentiation|
|endothelial cell fate commitment|
|negative regulation of glial cell apoptotic process|
|regulation of inner ear receptor cell differentiation|
|regulation of somitogenesis|
|regulation of mechanoreceptor differentiation|
|regulation of inner ear auditory receptor cell differentiation|
|blood vessel endothelial cell differentiation|
|marginal zone B cell differentiation|
|regulation of glial cell apoptotic process|
|Tat protein binding|
|loop of Henle development|
|left/right axis specification|
|regulation of timing of cell differentiation|
|epithelial cell fate commitment|
|cerebellar Purkinje cell layer morphogenesis|
|regulation of development, heterochronic|
|type B pancreatic cell development|
|negative regulation of epidermal cell differentiation|
|anatomical structure arrangement|
|regulation of vascular endothelial growth factor signaling pathway|
|negative regulation of cardiac muscle cell differentiation|
|segment specification|
|negative regulation of epidermis development|
|regulation of cellular response to vascular endothelial growth factor stimulus|
|negative regulation of interleukin-10 production|
|mature B cell differentiation involved in immune response|
|type B pancreatic cell differentiation|
|glandular epithelial cell development|
|enteroendocrine cell differentiation|
|left/right pattern formation|
|cerebellar cortex formation|
|negative regulation of cardiocyte differentiation|
|neuronal stem cell population maintenance|
|mature B cell differentiation|
|positive regulation of skeletal muscle tissue development|
|cerebellar Purkinje cell layer development|
|negative regulation of myoblast differentiation|
|clathrin-dependent endocytosis|
|Notch binding|
|cerebellar cortex morphogenesis|
|proximal/distal pattern formation|
|negative regulation of cardiac muscle tissue development|
|neuron fate specification|
|energy homeostasis|
|astrocyte development|
|regulation of cardiac muscle cell differentiation|
|cerebellum morphogenesis|
|endocrine pancreas development|
|negative regulation of striated muscle cell differentiation|
|glandular epithelial cell differentiation|
|positive regulation of sprouting angiogenesis|
|cell fate determination|
|negative regulation of epithelial cell differentiation|
|hindbrain morphogenesis|
|B cell activation involved in immune response|
|cerebellar cortex development|
|negative regulation of striated muscle tissue development|
|columnar/cuboidal epithelial cell development|
|regulation of skeletal muscle tissue development|
|retina morphogenesis in camera-type eye|
|negative regulation of muscle organ development|
|regulation of cardiocyte differentiation|
|negative regulation of muscle tissue development|
|regulation of interleukin-10 production|
|positive regulation of Notch signaling pathway|
|regulation of myoblast differentiation|
|astrocyte differentiation|
|negative regulation of muscle cell differentiation|
|sprouting angiogenesis|
|scaffold protein binding|
|heart looping|
|regulation of epidermal cell differentiation|
|embryonic pattern specification|
|adherens junction|
|neuron fate commitment|
|somitogenesis|
|embryonic heart tube morphogenesis|
|determination of heart left/right asymmetry|
|positive regulation of striated muscle tissue development|
|regulation of sprouting angiogenesis|
|positive regulation of muscle organ development|
|positive regulation of muscle tissue development|
|pancreas development|
|skin epidermis development|
|embryonic heart tube development|
|negative regulation of myeloid cell differentiation|
|nephron tubule development|
|regulation of cardiac muscle tissue development|
|renal tubule development|
|endothelial cell differentiation|
|somite development|
|axis specification|
|regulation of epidermis development|
|cell fate specification|
|segmentation|
|columnar/cuboidal epithelial cell differentiation|
|endothelium development|
|organ growth|
|nephron epithelium development|
|positive regulation of endocytosis|
|regulation of striated muscle cell differentiation|
|cerebellum development|
|regulation of Notch signaling pathway|
|glial cell development|
|spinal cord development|
|B cell differentiation|
|lymphocyte activation involved in immune response|
|metencephalon development|
|camera-type eye morphogenesis|
|determination of left/right symmetry|
|endocrine system development|
|determination of bilateral symmetry|
|skeletal muscle tissue development|
|specification of symmetry|
|nephron development|
|Notch signaling pathway|
|kidney epithelium development|
|regulation of embryonic development|
|regulation of striated muscle tissue development|
|skeletal muscle organ development|
|regulation of muscle tissue development|
|stem cell population maintenance|
|regulation of muscle organ development|
|negative regulation of hemopoiesis|
|maintenance of cell number|
|retina development in camera-type eye|
|regulation of epithelial cell differentiation|
|eye morphogenesis|
|hindbrain development|
|regulation of muscle cell differentiation|
|B cell activation|
|positive regulation of angiogenesis|
|regulation of cell division|
|glial cell differentiation|
|positive regulation of developmental growth|
|regulation of blood pressure|
|positive regulation of vasculature development|
|epithelial cell development|
|inner ear development|
|regulation of endocytosis|
|gliogenesis|
|anterior/posterior pattern specification|
|ear development|
|membrane raft|
|negative regulation of neuron differentiation|
|regulation of myeloid cell differentiation|
|lymphocyte differentiation|
|receptor-mediated endocytosis|
|cell fate commitment|
|heart morphogenesis|
|cytoplasmic vesicle|
|sensory organ morphogenesis|
|positive regulation of growth|
|kidney development|
|regulation of cellular response to growth factor stimulus|
|negative regulation of cytokine production|
|renal system development|
|striated muscle tissue development|
|regulation of angiogenesis|
|embryonic organ morphogenesis|
|negative regulation of neurogenesis|
|muscle organ development|
|muscle tissue development|
|epithelial tube morphogenesis|
|negative regulation of nervous system development|
|camera-type eye development|
|angiogenesis|
|urogenital system development|
|apical plasma membrane|
|regulation of vasculature development|
|multicellular organismal homeostasis|
|regulation of developmental growth|
|leukocyte differentiation|
|regionalization|
|negative regulation of cell development|
|eye development|
|visual system development|
|sensory system development|
|skin development|
|lymphocyte activation|
|developmental growth|
|blood circulation|
|growth|
|circulatory system process|
|blood vessel morphogenesis|
|epidermis development|
|morphogenesis of an epithelium|
|embryonic organ development|
|pattern specification process|
|negative regulation of immune system process|
|regulation of hemopoiesis|
|muscle structure development|
|blood vessel development|
|vasculature development|
|cardiovascular system development|
|heart development|
|sensory organ development|
|regulation of vesicle-mediated transport|
|endocytosis|
|hemopoiesis|
|tissue morphogenesis|
|embryonic morphogenesis|
|hematopoietic or lymphoid organ development|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|tube morphogenesis|
|regulation of neuron differentiation|
|regulation of growth|
|negative regulation of cell population proliferation|
|import into cell|
|regulation of cell adhesion|
|epithelial cell differentiation|
|regulation of cytokine production|
|negative regulation of cell differentiation|
|calcium ion binding|
|brain development|
|head development|
|regulation of neurogenesis|
|tube development|
|circulatory system development|
|negative regulation of apoptotic process|
|anatomical structure formation involved in morphogenesis|
|negative regulation of programmed cell death|
|positive regulation of cell population proliferation|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|negative regulation of developmental process|
|animal organ morphogenesis|
|embryo development|
|central nervous system development|
|positive regulation of transport|
|negative regulation of cell death|
|neuron differentiation|
|regulation of anatomical structure morphogenesis|
|cell activation|
|immune effector process|
|epithelium development|
|cell-cell signaling|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of developmental process|
|integral component of plasma membrane|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of cell population proliferation|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|extracellular region|
|vesicle-mediated transport|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|-1.93|
|[[:results:exp176|Apcin 50 to 100μM on day4 R04 exp176]]|-1.77|
|[[:results:exp48|Mubritinib 0.2μM R01 exp48]]|-1.77|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 2/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11197
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -1.17 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DLL1 Expression in NALM6 Cells: -1.17'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>