InterPro: IPR009138 Neural cell adhesion

Neural cell adhesion molecules (NCAM) are cell surface glycoproteins that share structural motifs related to immunoglobulin (Ig) and fibronectin type III (FNIII) domains. Expressed in neurons, glial cells and skeletal muscle, NCAM binds both homophilically and heterophilically, mediating processes such as neural cell growth and migration [1, 2, 3]. Polysialic acid binds to N-glycosylation sites in the Ig domains, affecting the binding of NCAM. Decreasing levels of sialynation on NCAM promotes aggregation, and is thought to be important in regulation of tissue stability [4].

The full length transcript contains (from N terminus to C terminus) five Ig domains, two FNIII domains, a transmembrane (TM) region and a cytosolic domain. Alternative splicing is known to generate at least four products with (apparent desialylated) molecular weights of 180, 140, 120 and 105kDa. The longer TM products are expressed in neurons (180 and 140kDa) and glial cells (140 kDa), whereas the 120kDa product is GPI-anchored on the surface of myotubes and the 105kDa product is secreted (for review see [4]). Further splice variation arises from a variable alternatively spliced exon (VASE) in the fourth Ig domain and a muscle-specific domain (MSD) between the two FNIII domains containing an O-glycosylation site.