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Description

EGF-like repeat and discoidin I-like domain-containing protein 3 (UniProt: O43854, also known as Developmentally-regulated endothelial cell locus 1 protein, Integrin-binding protein DEL1, Del-1) is encoded by the EDIL3 (also known as DEL1) gene (Gene ID: 10085) in human. Del-1 is a calcium-dependent glycoprotein that is secreted by endothelial cells and is shown to be expressed in a developmentally restricted pattern during embryogenesis. In adult tissues it is expressed in endothelial cells and in macrophages. Del-1 is reported to prevent apoptosis in endothelial cell subjected to TNF alpha, etoposide, and anoikis treatment. This anti-apoptotic effect is shown to be mediated specifically through binding of integrin alphav beta3 by the RGD motif. Del-1 expression is reported to be inversely related to that of IL-17 that is shown to inhibit Del-1 via a GSK-3beta and C/EBPb-dependent mechanism. This inhibitory action can be reversed at the PI3K/Akt signaling induced by D-resolvins. It serves as an endothelial cell-secreted homeostatic factor that regulates local inflammation in several tissues. It is reported to interfere with beta2-integrin-dependent inflammatory cell adhesion to endothelium and restricts transendothelial migration of neutrophils. Del-1 is synthesized with a signal peptide (aa 1-23), which is subsequently cleaved off in the mature form. It has three EGF-like domains in its N-terminal region. EGF-like domains 2 and 3 form a rigid rod via an interdomain calcium ion binding site, while the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1. Del-1 also has discoidin I-like domains at the C-terminal region that mediate its binding to phosphatidylserine. Two isoforms of Del-1 have been described that are produced by alternative splicing. (Ref.: Dasgupta, SK et al. (2012). Circulation 125 (13), 1664-1672, Wang, Z., et al. (2012). Surgery 151(2), 296-305, Maekawa, T et al. (2015). Nat. Commun. DOI: 10.1038/ncomms9272).