Identification of functionally important intracellular sequence motifs of carcinoembryonic antigen related cell adhesion molecule (CEACAM1) and CEACAM1-related proteins by multispecies sequence comparisons. The amino acid sequences encoded by cytoplasmic domain exons of CEACAM1 (A), CEACAM1-like members containing an immunoreceptor tyrosine-based activation motif (ITAM)-like motif from eutherians (B) and marsupials (C) from the indicated species were aligned. The sequences were separated according to exon borders. The names of the cytoplasmic domain encoding exons (Cyt) and the intron types (0, xxx-intron-xxx; 1, x-intron-xx; 2, xx-intron-x; xxx = codon) are indicated. The following potential motifs could be detected where x represents any amino acid, and slashes separate alternative amino acids (in one letter code) that may occupy a given position and are indicated below the corresponding sequences: an immunoreceptor tyrosine-based inhibition motif (ITIM) is defined by the sequence (I/L/V/S)xYxx(L/V), an immunoreceptor tyrosine-based switch motif (ITSM) by TxYxx(V/I), an ITAM by (D/E)xxYxxX(L/I)x6-8Yxx(L/I) and an endocytic, ITAM-like motif by Yxx(L/M/V/I/F). In catarrhinian primates and in platypus the ITSM has been switched to an ITIM. The opossum has two CEACAM1-like proteins one with two ITIM, and one with an ITIM and an ITSM. Note the characteristic split of the YxxL motif in the ITAM and ITAM-like motifs by phase 0 introns. The opossum ITAM domains could be predicted using an EST sequence [GenBank: EX196902] from the marsupial Macropus eugenii (tammar wallaby). An additional highly conserved motif (TEHKxS) and a conserved serine in the cytoplasmic domain of CEACAM1 proteins are boxed. For abbreviation of species names see Table 1.