Dll4 delta like canonical Notch ligand 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Dll4provided by MGI
Official Full Name: delta like canonical Notch ligand 4provided by MGI
Primary source: MGI:MGI:1859388
See related: Ensembl:ENSMUSG00000027314 AllianceGenome:MGI:1859388
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Delta4
Summary: Enables Notch binding activity. Involved in several processes, including blood vessel remodeling; circulatory system development; and regulation of Notch signaling pathway. Acts upstream of or within several processes, including Notch signaling pathway; angiogenesis; and negative regulation of blood vessel endothelial cell migration. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. Is expressed in several structures, including cardiovascular system; central nervous system; early conceptus; intestine; and sensory organ. Human ortholog(s) of this gene implicated in Adams-Oliver syndrome. Orthologous to human DLL4 (delta like canonical Notch ligand 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in lung adult (RPKM 41.8), subcutaneous fat pad adult (RPKM 15.0) and 16 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2; 2 E5

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (119156265..119166147)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (119325784..119335666)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells.
Title: Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells.
Dll4 Inhibition Promotes Graft Retention in Fat Grafting Enriched with Adipose-Derived Stem Cells.
Title: Dll4 Inhibition Promotes Graft Retention in Fat Grafting Enriched with Adipose-Derived Stem Cells.
The endothelial Dll4-muscular Notch2 axis regulates skeletal muscle mass.
Title: The endothelial Dll4-muscular Notch2 axis regulates skeletal muscle mass.
Delta-like 4 is required for pulmonary vascular arborization and alveolarization in the developing lung.
Title: Delta-like 4 is required for pulmonary vascular arborization and alveolarization in the developing lung.
Dll4 Blockade Promotes Angiogenesis in Nonhealing Wounds of Sox7-Deficient Mice.
Title: Dll4 Blockade Promotes Angiogenesis in Nonhealing Wounds of Sox7-Deficient Mice.
Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response.
Title: Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response.
Delta-like ligand 4-mediated Notch signaling controls proliferation of second heart field progenitor cells by regulating Fgf8 expression.
Title: Delta-like ligand 4-mediated Notch signaling controls proliferation of second heart field progenitor cells by regulating Fgf8 expression.
Canonical Notch ligands and Fringes have distinct effects on NOTCH1 and NOTCH2.
Title: Canonical Notch ligands and Fringes have distinct effects on NOTCH1 and NOTCH2.
Notch ligand Dll4 impairs cell recruitment to aortic clusters and limits blood stem cell generation.
Title: Notch ligand Dll4 impairs cell recruitment to aortic clusters and limits blood stem cell generation.
Slug regulates the Dll4-Notch-VEGFR2 axis to control endothelial cell activation and angiogenesis.
Title: Slug regulates the Dll4-Notch-VEGFR2 axis to control endothelial cell activation and angiogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (123)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

UniSTS:465450 (e-PCR)
- UniSTS:465450

Dll4 (e-PCR), detects polymorphism
- UniSTS:465450

UniSTS:465451 (e-PCR)
- UniSTS:465451

Dll4 (e-PCR), detects polymorphism
- UniSTS:465451

Dll4 (e-PCR), detects polymorphism
- UniSTS:496825

D2Mit104 (e-PCR), detects polymorphism
- UniSTS:128963

D2Dcr63 (e-PCR), detects polymorphism
- UniSTS:507622

Homology

Homologs of the Dll4 gene: The Dll4 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 497 organisms have orthologs with human gene Dll4
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables Notch binding	IDA Inferred from Direct Assay more info	PubMed
enables Notch binding	IPI Inferred from Physical Interaction more info	PubMed
enables Notch binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor ligand activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in Notch signaling involved in heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in T cell differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aortic valve morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in blood vessel lumenization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in blood vessel remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in branching involved in blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac atrium morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac ventricle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell communication	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to fibroblast growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to vascular endothelial growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in dorsal aorta morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of blood vessel endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell migration involved in sprouting angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nervous system development	IEA Inferred from Electronic Annotation more info
involved_in pericardium morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neural precursor cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neural retina development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of neurogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to stimulus	IEA Inferred from Electronic Annotation more info
involved_in ventral spinal cord interneuron fate commitment	ISO Inferred from Sequence Orthology more info
involved_in ventricular trabecula myocardium morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: delta-like protein 4

Names: delta-like 4; drosophila Delta homolog 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_019454.3 → NP_062327.2 delta-like protein 4 precursor

See identical proteins and their annotated locations for NP_062327.2

Status: VALIDATED

Source sequence(s)

AK052322, AL929318, BC049130

Consensus CDS

CCDS16600.1

UniProtKB/Swiss-Prot

Q9JHZ7, Q9JI71

Related

ENSMUSP00000099575.4, ENSMUST00000102517.4

Conserved Domains (3) summary

cd00054
Location:329 → 361

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

pfam01414
Location:156 → 218

DSL; Delta serrate ligand

pfam07657
Location:28 → 89

MNNL; N terminus of Notch ligand

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

119156265..119166147

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030251887.2 → XP_030107747.1 delta-like protein 4 isoform X1

Conserved Domains (1) summary

cd00054
Location:239 → 274

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...