Dll4 delta like canonical Notch ligand 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Dll4provided by RGD
Official Full Name: delta like canonical Notch ligand 4provided by RGD
Primary source: RGD:1309740
See related: Ensembl:ENSRNOG00000014011 AllianceGenome:RGD:1309740
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Predicted to enable Notch binding activity and receptor ligand activity. Involved in several processes, including cellular response to cholesterol; chondrocyte differentiation; and luteolysis. Predicted to be located in membrane. Predicted to be active in plasma membrane. Biomarker of diabetes mellitus; ischemia (multiple); lung carcinoma (multiple); polycystic kidney disease; and retinopathy of prematurity. Human ortholog(s) of this gene implicated in Adams-Oliver syndrome and limb ischemia. Orthologous to human DLL4 (delta like canonical Notch ligand 4). [provided by Alliance of Genome Resources, Jun 2025]
Expression: Biased expression in Lung (RPKM 143.2), Heart (RPKM 59.0) and 7 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 3q35

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (126770945..126780769)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (106317114..106327004)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (111135011..111146746)

Chromosome 3 - NC_086021.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Overexpression of miR-124 in astrocyte improves neurological deficits in rat with ischemic stroke via DLL4 modulation.
Title: Overexpression of miR-124 in astrocyte improves neurological deficits in rat with ischemic stroke via DLL4 modulation.
Inhibition of Dll4/Notch1 pathway promotes angiogenesis of Masquelet's induced membrane in rats.
Title: Inhibition of Dll4/Notch1 pathway promotes angiogenesis of Masquelet's induced membrane in rats.
Down-regulation of DLL4 expression is involved in chondrogenic differentiation of mesenchymal stem cells.
Title: MicroRNA-30a promotes chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression.
DLL4 expression increased in ischemic tissues and DLL4 expression was upregulated in capillary endothelial cells after ischemia.
Title: Inhibition of the Notch Pathway Promotes Flap Survival by Inducing Functional Neoangiogenesis.
The 2.3 angstrom resolution crystal structure of the interacting regions of the Notch1-DLL4 complex reveals a two-site, antiparallel binding orientation assisted by Notch1 O-linked glycosylation.
Title: Structural biology. Structural basis for Notch1 engagement of Delta-like 4.
Data suggest that DLL4, NOTCH1, and NOTCH4 are expressed in nuclei of small/large luteal cells of corpora lutea (CL) from pregnant rats and that luteolytic hormone PGF2alpha decreases the CL mRNA and protein expression of these NOTCH family members.
Title: Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat.

Submit: New GeneRIF Correction

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

d3mgh11 (e-PCR)
- UniSTS:120408

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info
enables Notch binding	IEA Inferred from Electronic Annotation more info
enables Notch binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables receptor ligand activity	IEA Inferred from Electronic Annotation more info
enables receptor ligand activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in T cell differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within angiogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in animal organ development	IEA Inferred from Electronic Annotation more info
involved_in aortic valve morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in aortic valve morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in blood vessel lumenization	IEA Inferred from Electronic Annotation more info
involved_in blood vessel lumenization	ISO Inferred from Sequence Orthology more info
involved_in blood vessel remodeling	IEA Inferred from Electronic Annotation more info
involved_in blood vessel remodeling	ISO Inferred from Sequence Orthology more info
involved_in branching involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in branching involved in blood vessel morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in cardiac atrium morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cardiac atrium morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in cardiac ventricle morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cardiac ventricle morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in cell communication	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cholesterol	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to fibroblast growth factor stimulus	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 hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to vascular endothelial growth factor stimulus	ISO Inferred from Sequence Orthology more info
involved_in chondrocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in dorsal aorta morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in dorsal aorta morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in luteolysis	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of Notch signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of blood vessel endothelial cell migration	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of blood vessel endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in pericardium morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in pericardium morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neural precursor cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neural precursor cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in regulation of neural retina development	IEA Inferred from Electronic Annotation more info
involved_in regulation of neural retina development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of neurogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of neurogenesis	ISO Inferred from Sequence Orthology more info
involved_in system development	IEA Inferred from Electronic Annotation more info
involved_in tissue development	IEA Inferred from Electronic Annotation more info
involved_in ventral spinal cord interneuron fate commitment	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	IEA Inferred from Electronic Annotation more info
involved_in ventricular trabecula myocardium morphogenesis	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: delta-like protein 4

Names: delta-like 4; delta4; 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_001107760.2 → NP_001101230.1 delta-like protein 4 isoform 2 precursor

See identical proteins and their annotated locations for NP_001101230.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000003

UniProtKB/TrEMBL

A0A8L2Q9H8, A6HPF0

Conserved Domains (3) summary

cd00054
Location:328 → 360

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:155 → 217

DSL; Delta serrate ligand

pfam07657
Location:27 → 88

MNNL; N terminus of Notch ligand
NM_001431709.1 → NP_001418638.1 delta-like protein 4 isoform 1 precursor

Status: VALIDATED

Source sequence(s)

JAXUCZ010000003

UniProtKB/Swiss-Prot

D3ZHH1

UniProtKB/TrEMBL

A0A8L2Q9H8

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086021.1 Reference GRCr8

Range

126770945..126780769

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006234765.4 → XP_006234827.1 delta-like protein 4 isoform X1

Related

ENSRNOP00000091766.1, ENSRNOT00000117478.2

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