DLL1 delta like canonical Notch ligand 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLL1provided by HGNC
Official Full Name: delta like canonical Notch ligand 1provided by HGNC
Primary source: HGNC:HGNC:2908
See related: Ensembl:ENSG00000198719 MIM:606582
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: DL1; Delta; DELTA1; NEDBAS
Summary: 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]
Expression: Ubiquitous expression in spleen (RPKM 12.9), brain (RPKM 6.2) and 22 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 6q27

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (170282200..170291078, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (170591288..170599815, complement)

Chromosome 6 - NC_000006.12 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
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?

The dissimilar effects of DLL1 downregulation observed amongst MCF-7, BT474, and MDA-MB-231 cells is likely due to their distinctive genetic and biologic characteristics, suggesting that DLL1 contributes to breast cancer through various mechanisms
Title: The Notch ligand DLL1 exerts carcinogenic features in human breast cancer cells.
DLL1 locus was marginally associated with TgAb levels in females.
Title: Genome-wide meta-analysis identifies novel gender specific loci associated with thyroid antibodies level in Croatians.
This study reveals NFIA as a pro-endocrine factor in the pancreas, acting to repress Mib1, inhibit Dll1 endocytosis and thus promote escape from Notch activation.
Title: Pancreatic Cell Fate Determination Relies on Notch Ligand Trafficking by NFIA.
It has been demonstrated that DLL1-dependent Notch signaling and GM-CSF cooperate to promote human dendritic cell differentiation.
Title: Large-Scale Human Dendritic Cell Differentiation Revealing Notch-Dependent Lineage Bifurcation and Heterogeneity.
CSF DLL1, VDBP and fetuin exhibited fair diagnostic performance for TBM diagnosis
Title: Delta-like 1 protein, vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis.
DLL1-mediated Notch signaling promotes luminal breast cancer
Title: Estrogen-dependent DLL1-mediated Notch signaling promotes luminal breast cancer.
This study produced recombinant DLL1-DE3, a novel soluble form of DLL1 protein, which contains the DSL domain and EGF1-3 repeats critical for Notch pathway activation. Cellular assays revealed recombinant DLL1-DE3 was biologically active as it increased expression of Notch-dependent genes in inducible pluripotent and breast cancer cells.
Title: Production and characterization of a novel Delta-like 1 functional unit as a tool for Notch pathway activation and generation of a specific antibody.
Abnormal DLL1 methylation and expression observed in early gastric lesions and in gastric cancers may be relevant to the pathogenesis of gastric cancer.
Title: Inverse Correlation between Methylation and Expression of the Delta-like Ligand 1 Gene in Gastric Cancer.
This study suggested that miR-34a-5p, DLL1 and the ATF2/ATF3/ATF4 signaling pathway-associated genes are the potential diagnostic and/or therapeutic targets for an effective chemotherapy of osteosarcoma.
Title: MiR-34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene.
miR-34a contributes to chondrocyte death, causing Osteoarthritis progression through DLL1 and modulation of the PI3K/AKT pathway.
Title: MiR-34a Enhances Chondrocyte Apoptosis, Senescence and Facilitates Development of Osteoarthritis by Targeting DLL1 and Regulating PI3K/AKT Pathway.

Submit: New GeneRIF Correction See all GeneRIFs (76)

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
NEURODEVELOPMENTAL DISORDER WITH NONSPECIFIC BRAIN ABNORMALITIES AND WITH OR WITHOUT SEIZURES MedGen: CN263062 OMIM: 618709 GeneReviews: Not available	not available

NHGRI GWAS Catalog

Description
A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. NHGRI GWA Catalog NHGRI GWA 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

Dll1 (e-PCR), detects polymorphism
- UniSTS:142854

DLL1_1441 (e-PCR)
- UniSTS:277165

DLL1_v480 (e-PCR)
- UniSTS:277165

Homology

Homologs of the DLL1 gene: The DLL1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 299 organisms have orthologs with human gene DLL1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
Notch binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Notch binding	IPI Inferred from Physical Interaction more info	PubMed
Tat protein binding	IPI Inferred from Physical Interaction more info	PubMed
calcium ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
scaffold protein binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
Notch signaling pathway	NAS Non-traceable Author Statement more info	PubMed
Notch signaling pathway involved in arterial endothelial cell fate commitment	ISS Inferred from Sequence or Structural Similarity more info
astrocyte development	ISS Inferred from Sequence or Structural Similarity more info
cell differentiation	TAS Traceable Author Statement more info	PubMed
cell fate determination	NAS Non-traceable Author Statement more info	PubMed
cerebellar Purkinje cell layer structural organization	ISS Inferred from Sequence or Structural Similarity more info
cerebellar molecular layer formation	ISS Inferred from Sequence or Structural Similarity more info
clathrin-dependent endocytosis	ISS Inferred from Sequence or Structural Similarity more info
compartment pattern specification	IEA Inferred from Electronic Annotation more info
determination of left/right symmetry	ISS Inferred from Sequence or Structural Similarity more info
endothelial tip cell fate specification	ISS Inferred from Sequence or Structural Similarity more info
energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
heart looping	ISS Inferred from Sequence or Structural Similarity more info
hemopoiesis	NAS Non-traceable Author Statement more info	PubMed
inner ear development	IEA Inferred from Electronic Annotation more info
lateral inhibition	ISS Inferred from Sequence or Structural Similarity more info
left/right axis specification	IEA Inferred from Electronic Annotation more info
loop of Henle development	IEA Inferred from Electronic Annotation more info
marginal zone B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of cardiac muscle cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of epidermal cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of epithelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of glial cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of inner ear auditory receptor cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of interleukin-10 production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of myeloid cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of myoblast differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
nephron development	ISS Inferred from Sequence or Structural Similarity more info
neuron fate specification	ISS Inferred from Sequence or Structural Similarity more info
neuronal stem cell population maintenance	IEP Inferred from Expression Pattern more info	PubMed
neuronal stem cell population maintenance	ISS Inferred from Sequence or Structural Similarity more info
organ growth	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of endocytosis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of skeletal muscle tissue growth	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of sprouting angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
proximal tubule development	IEA Inferred from Electronic Annotation more info
proximal/distal pattern formation	ISS Inferred from Sequence or Structural Similarity more info
regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info
regulation of cell adhesion	TAS Traceable Author Statement more info	PubMed
regulation of cell division	ISS Inferred from Sequence or Structural Similarity more info
regulation of growth	ISS Inferred from Sequence or Structural Similarity more info
regulation of neurogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of skeletal muscle tissue growth	ISS Inferred from Sequence or Structural Similarity more info
regulation of somitogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of vascular endothelial growth factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
retina development in camera-type eye	ISS Inferred from Sequence or Structural Similarity more info
retina morphogenesis in camera-type eye	ISS Inferred from Sequence or Structural Similarity more info
skeletal muscle tissue growth	ISS Inferred from Sequence or Structural Similarity more info
skin epidermis development	ISS Inferred from Sequence or Structural Similarity more info
somite specification	IEA Inferred from Electronic Annotation more info
somitogenesis	ISS Inferred from Sequence or Structural Similarity more info
spinal cord development	ISS Inferred from Sequence or Structural Similarity more info
type B pancreatic cell development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
adherens junction	ISS Inferred from Sequence or Structural Similarity more info
apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
integral component of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
membrane raft	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: delta-like protein 1

Names: H-Delta-1; drosophila Delta homolog 1; epididymis secretory sperm binding protein

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_027940.1 RefSeqGene

Range

4532..13404

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005618.4 → NP_005609.3 delta-like protein 1 precursor

See identical proteins and their annotated locations for NP_005609.3

Status: REVIEWED

Source sequence(s)

AL078605, AY358892, DA243552, DR000029

Consensus CDS

CCDS5313.1

UniProtKB/Swiss-Prot

O00548

Related

ENSP00000355718.3, ENST00000366756.4

Conserved Domains (3) summary

smart00051
Location:159 → 221

DSL; delta serrate ligand

cd00054
Location:329 → 364

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 ...

pfam07657
Location:22 → 92

MNNL; N terminus of Notch ligand

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

170282200..170291078 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005266934.4 → XP_005266991.1 delta-like protein 1 isoform X1

See identical proteins and their annotated locations for XP_005266991.1

Conserved Domains (3) summary

cd00054
Location:329 → 364

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:159 → 221

DSL; Delta serrate ligand

pfam07657
Location:22 → 91

MNNL; N terminus of Notch ligand