Sequence of a Cdna Clone Encoding the Polysialic Acid-Rich and Cytoplasmic Domains of the Neural Cell Adhesion Molecule N-CAM (amino Acid Sequence/nucleic Acid/hydrophobicity/modulation/transmembrane Glycoprotein)

Purified fractions of the neural cell-adhesion molecule N-CAM from embryonic chicken brain contain two similar polypeptides (Mr, 160,000 and 130,000), each contain- ing an amino-terminal external binding region, a carbohy- drate-rich central region, and a carboxyl-terminal region that is associated with the cell. Previous studies indicate that the two polypeptides arise by alternative splicing of mRNAs tran- scribed from a single gene. We report here the 3556-nucleotide sequence of a cDNA clone (pEC208) that encodes 964 amino acids from the carbohydrate and cell-associated domains of the larger N-CAM polypeptide followed by 664 nucleotides of 3' untranslated sequence. The predicted protein sequence con- tains attachment sites for polysialic acid-containing oligosac- charides, four tandem homologous regions of polypeptide resembling those seen in the immunoglobulin superfamily, and a single hydrophobic sequence that appears to be the mem- brane-spanning segment. The cytoplasmic domain carboxyl terminal to this segment includes a block of =250 amino acids present in the larger but not in the smaller N-CAM polypep- tide. We designate these the Id (large domain) polypeptide and the sd (small domain) polypeptide. The intracellular domains of the Id and sd polypeptides are likely to be critical for cell-surface modulation of N-CAM by interacting in a differ- ential fashion with other Intrinsic proteins or with the cytoskeleton.