A Comprehensive Phylogenetic and Structural Analysis of the Carcinoembryonic Antigen (CEA) Gene Family

Abstract

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin (Ig) superfamily and codes for a vast number of glycoproteins that differ greatly both in amino acid composition and function. The CEA family is divided into two groups, the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and the pregnancy-specific glycoproteins. The CEA family members are implicated in pleiotropic (patho)physiological functions including cell–cell adhesion, pregnancy, immunity, neovascularization, regulation of insulin homeostasis, and carcinogenesis. In general, the CEA-encoded proteins are composed of an extracellular region with Ig variable and constant-like domains and a cytoplasmic region containing signaling motifs. Of particular interest, the well-studied human and mouse CEA genes are arranged in clusters in a single chromosome. Taking into account this characteristic, we made an effort to reconstruct the evolutionary history of the CEA gene family. Toward this end, the publicly available genomes were searched extensively for CEA homologs. The domain organization of the retrieved protein sequences was analyzed, and, subsequently, comprehensive phylogenetic analyses of the entire length CEA homologous proteins were performed. A series of evolutionarily conserved amino acid residues, functionally important, were identified. The relative positioning of these residues on the modeled tertiary structure of novel CEA protein domains revealed that they are, also, spatially conserved. Furthermore, the chromosomal arrangement of CEA genes was examined, and it was found that the CEA genes are preserved in terms of position, transcriptional orientation, and number in all species under investigation.

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)

“…We will use numbering that starts after a signal peptide and designate the sites as 70, 77, and 81. Site 70 is in the dimer interface of the x-ray crystal structure 2GK2 (25) and is highly conserved within the family (34). The authors of this crystal structure did note that the putative N-linked glycosylation site, Asn-70, is located in the dimer interface of 2GK2 and may suppress dimer formation in the presence of glycans.…”

CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5 (carcinoembryonic antigen))

“…The CEACAM5 gene homologue is present in primates such as chimpazees, orangutans, macaques and marmosets, but not in rodents such as mice and rats (Pavlopoulou and Scorilas, 2014).…”

“…Out of 24 CEACAM family genes, twelve members (i.e., CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20 and CEACAM21) are expressed while the other 12 genes are pseudogenes (Pavlopoulou and Scorilas, 2014). All the CEACAM family genes are localized in the 19q13.2-19q13.4 region.…”

“…Out of 24 CEACAM family genes, twelve are pseudogenes and have been identified in the CEA family gene cluster (Pavlopoulou and Scorilas, 2014).…”

CEACAM Gene Family: A Circuitous Journey towards Metastasis in Breast Cancer

“…CEA gene family (CEA) belonging to immunoglobulin (Ig) supergene family was identified more than 50 years ago, comprises of 35 genes/pseudo genes (21 are protein coding) located on chromosome 19 (between q13.1-13.3), with wide range of patho-physiological functions [1,2]. Despite the over-expression of various CEA genes in very diverse cancers (breast, colon, prostate, pancreas, stomach, ovary, lung & medullary), its primary application as a serum biomarker is confined to the diagnosis & prognosis of colorectal cancers (CRC), and in the detection of liver metastasis.…”