CD226

CD226 (Cluster of Differentiation 226), PTA1 (outdated term, 'platelet and T cell activation antigen 1') or DNAM-1 (DNAX Accessory Molecule-1) is a ~65 kDa  immunoglobulin-like transmembrane glycoprotein expressed on the surface of natural killer cells, NK T cell, B cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes and T cells.

DNAM-1 gene CD226 is conserved between human and mice. In humans the CD226 gene is located on chromosome 18q22.3. In mice the CD226 gene is located on chromosome 18E4.

DNAM-1 is composed of three domains: an extracellular domain of 230 amino acids with two immunoglobin-like V-set domains and eight N-glycosylation sites, a transmembrane domain of 28 amino acids and a cytosolic domain of 60 amino acids containing four putative tyrosine residues and one serine residue for phosphorylation.

Upon engagement to its ligand, DNAM-1 is phosphorylated by protein kinase C. Then adhesive molecule LFA-1 crosslinks with DNAM-1 that results in recruitment of DNAM-1 to lipid rafts and promotes association with actin cytoskeleton. Cross-linking with LFA-1 also induce phosphorylation on Tyr¹²⁸ and Tyr¹¹³ by Fyn Src kinase.

DNAM-1 and CD244 together promotes phosphorylation of SH2 domain of SLP-76. This leads to activation of phospholipase Cγ2, Ca²⁺ influx, cytoskeletal reorganization, degranulation, and secretion.

DNAM-1 mediates cellular adhesion to other cells bearing its ligands, nectin molecule CD112 and nectin-like protein CD155, that are broadly distributed on normal neuronal, epithelial, fibroblastic cells, dendritic cells, monocytes and on infected or transformed cells.

DNAM-1 promotes lymphocyte signaling, lymphokine secretion and cytotoxicity of NK cells and cytotoxic CD8+ T lymphocytes. Cross-linking of DNAM-1 with antibodies causes cellular activation.

DNAM-1 participates on platelets activation and aggregation.