Delta and Notch-like epidermal growth factor-related receptor (DNER)

Delta and Notch-like epidermal growth factor-related receptor (DNER) is a single-pass transmembrane protein characterized by ten EGF-like repeats in its extracellular domain, which share similarities with Notch ligands[1][2][3]. DNER is predominantly expressed in the central nervous system, where it localizes to dendritic plasma membranes of post-mitotic neurons (e.g., cortical, hippocampal pyramidal neurons, cerebellar granule and Purkinje cells) and plays roles in establishing neuronal polarity, dendritogenesis, and neuron-glia interactions[1][3]. DNER enables Notch binding activity and influences cell sorting and targeting through its cytoplasmic domain’s tyrosine-based motifs[1][3]. Beyond the CNS, DNER is also expressed in pancreatic β-cells, where it regulates cell-cell adhesion (via N-CAM, E-cadherin, Connexin 36), islet morphology, cytoskeletal remodeling (F-actin dynamics), and glucose-stimulated insulin secretion, implicating it in blood glucose homeostasis and as a genetic risk factor for type 2 diabetes[2][3]. In addition, DNER overexpression has been associated with tumor proliferation and invasiveness in hepatocellular carcinoma, and its expression serves as a biomarker for certain neuroendocrine cancer signatures[3].

Other names

Delta/notch-like EGF repeat containingDNERBETUNQ262/PRO299UNQ26delta and Notch-like epidermal growth factor-related receptorH_NH0150O02.1WUGSC:H_NH0150O02.1delta-notch-like EGF repeat-containing transmembrane

DNER modulates the Notch pathway. In the context of cancer, it activates the PI3K/AKT pathway. It also regulates cell-cell adhesion proteins (N-CAM, E-cadherin), which affects insulin secretion and glucose homeostasis.