DLL4

Protein identityUniProt · HPA

UniProt accession

Q9NR61

Gene

DLL4

Ensembl

ENSG00000128917

Chromosome

15

Canonical length

685 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

685 residues, UniProt reviewed canonical sequence.

>Q9NR61|DLL4
     1  MAAASRSASG WALLLLVALW QQRAAGSGVF QLQLQEFINE RGVLASGRPC EPGCRTFFRV
    61  CLKHFQAVVS PGPCTFGTVS TPVLGTNSFA VRDDSSGGGR NPLQLPFNFT WPGTFSLIIE
   121  AWHAPGDDLR PEALPPDALI SKIAIQGSLA VGQNWLLDEQ TSTLTRLRYS YRVICSDNYY
   181  GDNCSRLCKK RNDHFGHYVC QPDGNLSCLP GWTGEYCQQP ICLSGCHEQN GYCSKPAECL
   241  CRPGWQGRLC NECIPHNGCR HGTCSTPWQC TCDEGWGGLF CDQDLNYCTH HSPCKNGATC
   301  SNSGQRSYTC TCRPGYTGVD CELELSECDS NPCRNGGSCK DQEDGYHCLC PPGYYGLHCE
   361  HSTLSCADSP CFNGGSCRER NQGANYACEC PPNFTGSNCE KKVDRCTSNP CANGGQCLNR
   421  GPSRMCRCRP GFTGTYCELH VSDCARNPCA HGGTCHDLEN GLMCTCPAGF SGRRCEVRTS
   481  IDACASSPCF NRATCYTDLS TDTFVCNCPY GFVGSRCEFP VGLPPSFPWV AVSLGVGLAV
   541  LLVLLGMVAV AVRQLRLRRP DDGSREAMNN LSDFQKDNLI PAAQLKNTNQ KKELEVDCGL
   601  DKSNCGKQQN HTLDYNLAPG PLGRGTMPGK FPHSDKSLGE KAPLRLHSEK PECRISAICS
   661  PRDSMYQSVC LISEERNECV IATEV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DLL4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DLL4.

Disease | AllUniProt

Conditions DLL4 is implicated in, by any mechanism.

• Adams-Oliver syndrome 6 (AOS6) MIM:616589

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 342 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Adams-Oliver syndrome 6
• Adams-Oliver syndrome
• DLL4-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.19

gnomAD pLI

1

gnomAD missense Z

2.71

DepMap mean gene effect

-0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• aortic valve morphogenesis
• blood vessel lumenization
• blood vessel remodeling
• branching involved in blood vessel morphogenesis
• cardiac atrium morphogenesis
• cardiac ventricle morphogenesis
• cellular response to fibroblast growth factor stimulus
• cellular response to vascular endothelial growth factor stimulus
• dorsal aorta morphogenesis
• negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
• negative regulation of cell migration involved in sprouting angiogenesis
• negative regulation of cell population proliferation
• negative regulation of endothelial cell migration
• negative regulation of gene expression
• negative regulation of Notch signaling pathway
• negative regulation of transcription by RNA polymerase II
• Notch signaling pathway
• pericardium morphogenesis
• positive regulation of gene expression
• positive regulation of neural precursor cell proliferation
• positive regulation of Notch signaling pathway
• regulation of neural retina development
• regulation of neurogenesis
• signal transduction
• T cell differentiation
• ventral spinal cord interneuron fate commitment
• ventricular trabecula myocardium morphogenesis
• visual perception

Molecular functions

• calcium ion binding
• Notch binding
• receptor ligand activity

Cellular components

• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• Delta/Serrate/lag-2 (DSL) protein
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• Notch ligand, N-terminal domain
• EGF-like domain
• Delta serrate ligand
• N terminus of Notch ligand C2-like domain
• Delta-like/Jagged, EGF-like domain

KeywordsUniProt

• Angiogenesis
• Cell membrane
• Developmental protein
• Differentiation
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Membrane
• Neurogenesis
• Notch signaling pathway
• Repeat
• Sensory transduction
• Signal
• Transmembrane
• Transmembrane helix
• Vision

InteractionsUniProt · HPA

Protein binding partners of DLL4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NOTCH4
• NEURL1B