Component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. Also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. Upon epithelial CXADR-binding, JAML induces downstream cell signaling events in gamma-delta T-cells through PI3-kinase and MAP kinases. It results in proliferation and production of cytokines and growth factors by T-cells that in turn stimulate epithelial tissues repair. (Microbial infection) Acts as a receptor for adenovirus type C. (Microbial infection) Acts as a receptor for Coxsackievirus B1 to B6. Monomer. May form homodimer. Interacts with LNX, MAGI1, DLG4, PRKCABP, TJP1 and CTNNB1. Interacts with MPDZ; recruits MPDZ to intercellular contact sites. Interacts with JAML (homodimeric form). Secreted isoform 3, isoform 4 and isoform 5 can interact with the extracellular domain of the receptor. (Microbial infection) Interacts with adenovirus subgroups A, C, D, E and F fiber proteins as well as coxsackievirus B1, B2, B3, B4, B5 and B6 capsid proteins (PubMed:14978041, PubMed:9733828, PubMed:10666333, PubMed:10814575, PubMed:12297051, PubMed:10567268). In epithelial cells localizes to the apical junction complex composed of tight and adherens junctions (PubMed:12297051). In airway epithelial cells localized to basolateral membrane but not to apical surface (PubMed:11316797). Expressed in pancreas, brain, heart, small intestine, testis, prostate and at a lower level in liver and lung. Isoform 5 is ubiquitously expressed. Isoform 3 is expressed in heart, lung and pancreas. In skeletal muscle, isoform 1 is found at the neuromuscular junction and isoform 2 is found in blood vessels. In cardiac muscle, isoform 1 and isoform 2 are found at intercalated disks. In heart expressed in subendothelial layers of the vessel wall but not in the luminal endothelial surface. Expression is elevated in hearts with dilated cardiomyopathy. The Ig-like C2-type 1 domain mediates homodimerization and interaction with JAML. The PDZ-binding motif mediates interaction with MPDZ and MAGI1. N-glycosylated. Palmitoylated on Cys-259 and/or Cys-260; required for proper localization to the plasma membrane.