|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|65 / 65|
|CD226 is expressed on the majority of T and NK cells, platelets, monocytes, peripheral blood T lymphocytes and a subset of B cells and thymocytes, as well as activated HUVEC. Expression is not detected on granulocytes and erythrocytes. A soluble form (MW 50 kDa) of CD226 is present in normal serum and the supernatant of cultured activated T cells. CD226 is present on the MLA-144 gibbon cell line and activated monkey T cells.|
|MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gen superfamily.|
CD226 is a single-pass type-1 adhesion glycoprotein. It contains an 18 aa leader sequence, a 232 aa extracellular domain which contains 2 Ig-like C2-type domains, 8 potential N-linked and 3 O-linked glycosylation sites, a 25 aa transmembrane domain and a 61 aa cytoplasmic region with 3 potential tyrosine phosphorylation sites for protein kinase C and casein kinase II and Fyn. Phosphorylation of cytoplasmic serine is required for the interaction of CD226 with CD11a/CD18 (LFA-1). A 50 kDa soluble form of CD226 is detectable in normal serum and culture supernatent of activated T cells. CD226 mediates cellular adhesion to other cells bearing an unidentified ligand. Cross-linking of CD226 with antibodies causes cell activation.
PI of 3.5-4.2 is purified from platelets. On peripheral blood lymphocytes, CD226 has an apparent molecular weight of ~65 kDa when analyzed by SDS-PAGE using either reducing or non-reducing conditions.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD226 contains 8 potential sites for N-linked glycosylation and the protein is modified by N-linked sugars. CD226 can be phosphorylated on serine 329 and tyrosine 322.
|LIGANDS AND MOLECULES ASSOCIATED WITH CD226|
CD226 associates with LFA-1. COS cells transfected with CD226 bind to a variety of hematopoietic and non-hematopoietic cells indicating the presence of a widely distributed ligand. In anti-CD3 stimulated T cells, CD226 is co-immunoprecipitated with the CD11a/CD18 integrin. Serine phosphorylation at Ser-329 of CD226 is required for this interaction. CD155 and CD112 are ligands for CD226.
|CD226 can mediate the attachment of transfected cells to presumed ligand-bearing cells in a process independent of divalent cations but is regulated by serine 329 phosphorylation by protein kinase C. It associates with LFA-1 and actin-binding 4.1 G. Intact antibody and Fab1, 2 fragments of some mAb and polyclonal antibodies to CD226 inhibit the generation of CTL in a mixed lymphocyte culture and restimulation of allergenic cytotoxic T cell clones. The mAb to CD226 initiates platelet activation and aggregation in a process dependent on the Fc receptor and protein kinase C activation. Depending on the experimental conditions some mAb can trigger NK or T cell-mediated cytotoxicity, or can inhibit the cytolysis of some tumor target cells. CD226 is involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphocyte secretion mediated by CTL. It is also involved in the activation of T or NK cell cytotoxicity and leukocyte adhesion. CD226 mediates cellular adhesion to other cells bearing an undentified ligand and cross-linking CD226 with antibodies causing cellular activation. CD226 has a cytolytic function mediated by CTL and NK cells, platelets and T cell activation antigen 1. CD226 mAb blocks NK and cytotoxic T cell killing. Crosslinking of CD226 causes phosphorylation of tyrosine residues in DNAX accessory molecule-1 (DNAM-1) indicating a possible role in signaling.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD226 IN INTACT ANIMAL
CD226 expression on T cells is increased in patients with some autoimmune diseases and viral infections. CD226 is expressed but apparently does not signal in a patient with leukocyte adhesion deficiency (LAD) which is caused by a mutation of the CD18 gene. Cross-linking CD226 with mAbs in normal, healthy individuals triggers NK cell-mediated cytotoxicity, however, this activity is absent in a patient with LAD. Restoration of CD11a/CD18 expression in LAD, NK cells by retroviral transduction with CD18 cDNA resulted in the reconstitution of the CD226 function in these NK cells. The platelets from a patient with Glanzmann's thrombasthenia is caused by the absence of GPIIb-IIIa expression and does not show activation and aggregation stimulated by LeoA1 mAb.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD226: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD226
Database accession numbers
Revised June 25, 2008