DLL4 delta like canonical Notch ligand 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLL4provided by HGNC
Official Full Name: delta like canonical Notch ligand 4provided by HGNC
Primary source: HGNC:HGNC:2910
See related: Ensembl:ENSG00000128917 MIM:605185; AllianceGenome:HGNC:2910
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AOS6; delta4; hdelta2
Summary: This gene is a homolog of the Drosophila delta gene. The delta gene family encodes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. [provided by RefSeq, Jul 2008]
Expression: Broad expression in placenta (RPKM 11.5), fat (RPKM 11.2) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q15.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (40929340..40939073)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (38735323..38745058)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (41221538..41231271)

Chromosome 15 - NC_000015.10 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Circ_0006476 modulates macrophage apoptosis through the miR-3074-5p/DLL4 axis: implications for Notch signalling pathway regulation in cardiovascular disease.
Title: Circ_0006476 modulates macrophage apoptosis through the miR-3074-5p/DLL4 axis: implications for Notch signalling pathway regulation in cardiovascular disease.
Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
Title: Astrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
KLF13 restrains Dll4-muscular Notch2 axis to improve the muscle atrophy.
Title: KLF13 restrains Dll4-muscular Notch2 axis to improve the muscle atrophy.
Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling.
Title: Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling.
DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
Title: DLL4/Notch3/WNT5B axis mediates bidirectional prometastatic crosstalk between melanoma and lymphatic endothelial cells.
DLL4 promotes partial endothelial-to-mesenchymal transition at atherosclerosis-prone regions of arteries.
Title: DLL4 promotes partial endothelial-to-mesenchymal transition at atherosclerosis-prone regions of arteries.
Endothelial DLL4 Is an Adipose Depot-Specific Fasting Sensor Regulating Fatty Acid Fluxes.
Title: Endothelial DLL4 Is an Adipose Depot-Specific Fasting Sensor Regulating Fatty Acid Fluxes.
DLL4-Notch signalling in acute-on-chronic liver failure: State of the art and perspectives.
Title: DLL4-Notch signalling in acute-on-chronic liver failure: State of the art and perspectives.
Expressions and Prognostic Values of Notch3 and DLL4 in Human Breast Cancer.
Title: Expressions and Prognostic Values of Notch3 and DLL4 in Human Breast Cancer.
Low HES-1 and positive DLL4 expression predicts poor prognosis of colorectal cancers.
Title: Low HES-1 and positive DLL4 expression predicts poor prognosis of colorectal cancers.

Submit: New GeneRIF Correction See all GeneRIFs (142)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Adams-Oliver syndrome 6 MedGen: C4225271 OMIM: 616589 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:70152

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

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

PMC316657P1 (e-PCR)
- UniSTS:273027

PMC316657P2 (e-PCR)
- UniSTS:273028

DLL4_593 (e-PCR)
- UniSTS:277166

RH78211 (e-PCR)
- UniSTS:84154

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info
enables Notch binding	IPI Inferred from Physical Interaction more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed

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

Component	Evidence Code	Pubs
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
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 4; delta ligand 4; delta-like 4 homolog; delta-like 4 protein; drosophila Delta homolog 4; notch ligand DLL4; notch ligand delta-2

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.

Genomic

NG_046974.1 RefSeqGene

Range

5008..14741

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1268

mRNA and Protein(s)

NM_019074.4 → NP_061947.1 delta-like protein 4 precursor

See identical proteins and their annotated locations for NP_061947.1

Status: REVIEWED

Source sequence(s)

AB036931, AI478830, BC106950, DA089757, HY291308

Consensus CDS

CCDS45232.1

UniProtKB/Swiss-Prot

Q3KP23, Q9NQT9, Q9NR61

UniProtKB/TrEMBL

B2R9L8

Related

ENSP00000249749.5, ENST00000249749.7

Conserved Domains (3) summary

cd00054
Location:327 → 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