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

Gene ID: 54567, updated on 26-May-2016
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 HPRD:05540; MIM:605185; Vega:OTTHUMG00000172511
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; 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]
Orthologs
Location:
15q14
Exon count:
11
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 15 NC_000015.10 (40929333..40939060)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (41221531..41231258)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene VPS18, CORVET/HOPS core subunit Neighboring gene uncharacterized LOC105370943 Neighboring gene iron-sulfur cluster assembly 1 pseudogene 4 Neighboring gene ChaC glutathione specific gamma-glutamylcyclotransferase 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Adams-Oliver syndrome 6
MedGen: CN233136 OMIM: 616589 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
NHGRI GWA Catalog
  • Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystem (from REACTOME)
    Activated NOTCH1 Transmits Signal to the Nucleus, organism-specific biosystemMature NOTCH1 heterodimer on the cell surface is activated by one of its ligands: DLL1 (Cordle et al. 2008, Jarriault et al. 1998), DLL4 (Benedito et al. 2009), JAG1 (Li et al. 1998, Benedito et al. ...
  • Constitutive Signaling by NOTCH1 HD Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 HD Domain Mutants, organism-specific biosystemThe heterodimerization (HD) domain of NOTCH1, responsible for association of NOTCH1 extracellular and transmembrane regions after furin-mediated cleavage of NOTCH1 precursor, is one of the hotspots f...
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants, organism-specific biosystemWhen found in cis, HD and PEST domain mutations act synergistically, increasing NOTCH1 transcriptional activity up to ~40-fold, compared with up to ~10-fold and up to ~2-fold increase with HD mutatio...
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 PEST Domain Mutants, organism-specific biosystemAs NOTCH1 PEST domain is intracellular, NOTCH1 PEST domain mutants are expected to behave as the wild-type NOTCH1 with respect to ligand binding and proteolytic cleavage mediated activation of signal...
  • Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, organism-specific biosystemNOTCH1 t(7;9)(NOTCH1:M1580_K2555) mutant is expressed in a small subset of T-cell acute lymphoblastic leukemia (T-ALL) patients. This mutant protein results from a translocation that joins a portion ...
  • Delta-Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Delta-Notch Signaling Pathway, organism-specific biosystemThere are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric protei...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystem (from REACTOME)
    NOTCH2 Activation and Transmission of Signal to the Nucleus, organism-specific biosystemSimilar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004...
  • Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
    Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch signaling, organism-specific biosystem (from KEGG)
    Notch signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling, conserved biosystem (from KEGG)
    Notch signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
  • Notch signaling pathway, organism-specific biosystem (from KEGG)
    Notch signaling pathway, organism-specific biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • Notch signaling pathway, conserved biosystem (from KEGG)
    Notch signaling pathway, conserved biosystemThe Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in all metazoan organisms in the Animal kingdom. The Notch pro...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by NOTCH, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH, organism-specific biosystemThe Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For exam...
  • Signaling by NOTCH1, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1, organism-specific biosystemNOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.NOTCH1 receptor presented on the plasma membrane is activated by a me...
  • Signaling by NOTCH1 HD Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 HD Domain Mutants in Cancer, organism-specific biosystemNOTCH1 heterodimerization domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL) (Weng et al. 2004) and result in constitutive activity of NOTCH1 mutants (Malecki et al....
  • Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer, organism-specific biosystemMutations in the heterodimerization domain (HD) and PEST domain of NOTCH1 are frequently found in cis in T-cell acute lymphoblastic leukemia. While HD mutations alone result in up to ~10-fold increas...
  • Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 PEST Domain Mutants in Cancer, organism-specific biosystemNOTCH1 PEST domain mutations are frequently found in T-cell acute lymphoblastic leukemia (T-ALL). PEST domain mutations interfere with ubiquitination-mediated NOTCH1 downregulation and result in prol...
  • Signaling by NOTCH1 in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 in Cancer, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). This tra...
  • Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant, organism-specific biosystemHuman NOTCH1 was cloned as a chromosome 9 gene, translocated to the T-cell beta receptor (TCBR) promoter on chromosome 7 in T-cell acute lymphoblastic leukemia (T-ALL) (Ellisen et al. 1991). The tran...
  • Signaling by NOTCH2, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH2, organism-specific biosystemNOTCH2 is activated by binding Delta-like and Jagged ligands (DLL/JAG) expressed in trans on neighboring cells (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). In trans ...
  • Signaling by NOTCH3, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH3, organism-specific biosystemSimilar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleav...
  • Signaling by NOTCH4, organism-specific biosystem (from REACTOME)
    Signaling by NOTCH4, organism-specific biosystemSimilar to NOTCH1, NOTCH4 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH4, first by ADAM10 at the S2 cleav...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC126344

Gene Ontology Provided by GOA

Function Evidence Code Pubs
Notch binding IEA
Inferred from Electronic Annotation
more info
 
calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
Notch receptor processing TAS
Traceable Author Statement
more info
 
Notch signaling involved in heart development ISS
Inferred from Sequence or Structural Similarity
more info
 
Notch signaling pathway TAS
Traceable Author Statement
more info
 
T cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
blood circulation TAS
Traceable Author Statement
more info
PubMed 
blood vessel lumenization IEA
Inferred from Electronic Annotation
more info
 
blood vessel remodeling ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac atrium morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac ventricle morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to fibroblast growth factor stimulus IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to vascular endothelial growth factor stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
dorsal aorta morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of Notch signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell migration involved in sprouting angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell migration involved in sprouting angiogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of endothelial cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription from RNA polymerase II promoter ISS
Inferred from Sequence or Structural Similarity
more info
 
patterning of blood vessels ISS
Inferred from Sequence or Structural Similarity
more info
 
pericardium morphogenesis 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 gene expression IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of neural precursor cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of neural retina development ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of neurogenesis IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
ventral spinal cord interneuron fate commitment IMP
Inferred from Mutant Phenotype
more info
PubMed 
ventricular trabecula myocardium morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
visual perception IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
delta-like protein 4
Names
delta 4
delta ligand 4
delta-like 4 homolog
delta-like 4 protein
delta4
drosophila Delta homolog 4
notch ligand DLL4
notch ligand delta-2

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

  1. NG_046974.1 RefSeqGene

    Range
    5001..14728
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_019074.3NP_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
    Consensus CDS
    CCDS45232.1
    UniProtKB/Swiss-Prot
    Q9NR61
    Related
    ENSP00000249749, OTTHUMP00000248570, ENST00000249749, OTTHUMT00000418859
    Conserved Domains (3) summary
    cd00054
    Location:327360
    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:2691
    MNNL; N terminus of Notch ligand
    cl19567
    Location:155217
    DSL; Delta serrate ligand

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p2 Primary Assembly

    Range
    40929333..40939060
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018926.2 Alternate CHM1_1.1

    Range
    41339420..41349204
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)