Expansion of ITAM-bearing CEACAM1-related CEA family members in dog. (A) Relationship of transmembrane domain and hydrophobic GPI signal peptide-encoding exon sequences of human and canine CEA family members. The nucleotide sequences of the transmembrane domain exons and exons encoding the GPI signal peptides of human CEA family members were aligned and the results displayed as rooted dendrogram. Three groups can be discriminated: the transmembrane domain sequences of the orthologous genes (CEACAM18, CEACAM19 and CEACAM20) form pairs, CEACAM3, CEACAM4 and CEACAM21 sequences are clustered together with the dog CEACAM1-related sequences (red box) and the GPI signal sequences are most closely related to the CEACAM1 transmembrane exon sequence (blue box). All transmembrane domain exons boxed red are followed by exons encoding cytoplasmic domains with an ITAM except for CEACAM21 and CEACAM29. Their cytoplasmic domains terminate prematurely due to a stop codon at the end of cytoplasmic domain exon 2 and loss of the splice donor site in cytoplasmic domain exon 3 with subsequent read-through into the following intron, respectively. (B) Amino acid sequence alignment of cytoplasmic domains (encoded by the cytoplasmic domain exons Cyt1-Cyt4) from dog CEACAM1-related proteins. The ITAM consensus sequence is indicated below and the intron phases above the sequences. Note the typical split by a phase 0 intron of the first YxxL motif of the ITAM motifs. Hsa, Homo sapiens; Cfa, Canis familiaris.