Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis.
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Biallelic DLL3 mutations, including truncations of conserved extracellular domains and a missense change in the fifth EGF repeat, cause autosomal recessive spondylocostal dysostosis in humans.
"Two of the mutations predict truncations within conserved extracellular domains. The third is a missense mutation in a highly conserved glycine residue of the fifth epidermal growth factor (EGF) repeat"
Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo.
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DLL3 cannot substitute for DLL1 in mice and does not activate Notch in Drosophila wing discs; endogenous DLL3 is predominantly Golgi-localized while DLL1 is at the surface of the same presomitic mesoderm cells.
"In contrast to endogenous DLL1 located on the surface of presomitic mesoderm cells, we find endogenous DLL3 predominantly in the Golgi apparatus."
Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis.
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DLL3 binds Notch1 in the late endocytic compartment and targets newly synthesised receptor for lysosomal degradation, cis-inhibiting Notch signalling in the presomitic mesoderm.
"This suggests for the first time a mechanism for Dll3-mediated cis-inhibition of Notch signalling, with Dll3 targeting newly synthesized Notch1 for lysosomal degradation prior to post-translational processing and cell surface presentation of the receptor."
A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.
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DLL3 is detectable on the surface of SCLC and LCNEC tumour cells and on non-permeabilised engineered cells, showing that the protein is not obligately confined to the Golgi when overexpressed.
"establishing that DLL3 protein can localize to the cell surface and is not necessarily confined to the Golgi"
Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.
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In normal cells DLL3 is largely confined to Golgi and cytoplasmic vesicles, while in SCLC it is upregulated and traffics to the plasma membrane.
"DLL3 expression is low and mainly confined to the Golgi apparatus and cytoplasmic vesicles in normal cells but is upregulated and traffics to the surface of SCLC cells"