Structure, function and exon organization of CD44. (A) Structure and functions of CD44 glycoprotein [1–4]. CD44 structure. The heavy and intermediate black tracks represent the conserved N-terminal region of the extracellular domain, the transmembrane region and the cytoplasmic tail. The heavy black track at the N terminus represents the link module. The thin black track represents the nonconserved membrane-proximal region. Filled circles, potential N-linked glycosylation sites; open circles, potential O-linked glycosylation sites; filled diamonds, sites for glycosaminoglycan (chondroitin sulfate [CS] or heparan sulfate [HS]) attachments (the HS of exon v3 is involved in the binding of growth factors); P, potential sites for phosphorylation. Insets: CD44 functions. Inset a, the basic cluster and the amino acids critical to HA binding. Inset b, binding sites for ezrin radixin moesin (ERM) and for ankyrin as well as two phosphorylation sites; the location of the sugars and the functional sites is for illustrative purposes only. (B) CD44 isoforms: exon map. Filled circles represent the constant-region exons; open circles represent exons that can be inserted by alternative splicing, resulting in the generation of the variable region. Note that exon v1 is not expressed in human CD44. LP, leader peptide-encoding exon; TM, transmembrane-encoding exon; CT, cytoplasmic tail-encoding exon. (C) Examples of alternatively spliced transcripts: 1, standard CD44, which lacks the entire variable region; 2, pMeta-1 (CD44v4–v7; exons v4, v5, v6 and v7 are inserted in tandem between exons 5 and 17 [residues 204 and 205]); 3, pMeta-2 (CD44v6,v7) (pMeta-1 and pMeta-2 are known as metastatic CD44 because their cDNA confers, upon transfection, metastatic potential on nonmetastatic rat tumor cells); 4, epithelial CD44 (CD44v8–v10); 5, keratinocyte CD44 (CD44v3–v10). This figure is reproduced from Wiley Encyclopedia of Molecular Medicine, CD44 entry by D Naor and S Nedvetzki, vol 5, pp 619–624 (2002), by permission of John Wiley and Sons, Inc.