Carcinoembryonic antigen family: characterization of cDNAs coding for NCA and CEA and suggestion of nonrandom sequence variation in their conserved loop-domains.

We have isolated cDNAs for carcinoembryonic antigen (CEA) and for a normal cross-reacting antigen (NCA) and report here their nucleotide and derived amino acid sequences. Our data show that both the CEA and NCA polypeptides are organized into extracellular domains, some with cysteine-linked loops, that share extensive sequence homology (approximately 78% overall) with each other and appear similar to immunoglobulin superfamily members. A major difference between the two apoproteins is the presence of a single loop-domain in NCA compared to three tandemly repeated loop-domains in CEA. Sequence comparisons between the extracellular domains of CEA and NCA show that the N-terminal and adjacent loop domains of each apoprotein have high homology (85-90%) to each other, while comparison of loop-domain regions reveals a possible nonrandom distribution of base changes and altered amino acids near certain cysteine residues that are inferred to be involved in forming disulfide loops. Both apoproteins show high identity in their hydrophobic C-termini that are reminiscent of the type of transmembrane tails seen in proteins that potentiate signal transduction. These findings, coupled with distinct expression profiles of CEA and NCA mRNAs, suggest that these apoproteins may function as unique cell-surface molecules mediating cell-specific interactions in normal and neoplastic cells.