CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein))

Note	The locus is complex, and it produces several proteins via alternative splicing.
	Genomic structure of human CEACAM1. Open and closed boxes indicate untranslated regions and coding regions (exons) of CEACAM1 gene, respectively. The ATG initiation codon is located in the first exon, and the TGA termination codon is located in exon 9. N, A1, B1 and A2; Ig domains, TM; transmembrane domain, C; cytoplasmic domain.
Description	The gene is composed of 9 exons spanning in a region of 23,140 bp (Localized from 47,724,479 to 47,703,298 from pter).
Transcription	Human CEACAM1 consists of 9 exons that can be alternatively spliced to generate 11 different isoforms. The gene contains 19 different introns, and the sequence is supported by 286 sequences from 262 cDNA clones. The transcripts differ by truncation of the N-terminus, truncation of the C-terminus, presence or absence of a cassette exon, common exons with different boundaries. Among various types of isoforms, the full-length nature of two alternative transcripts (NM_001024912.1, NM_001712.3) has been determined.
Pseudogene	Eleven pseudogenes of the CEA cell adhesion molecule subgroup are found in the cluster of the two subgroups of the CEA family (the CEA cell adhesion molecules and the pregnancy-specific glycoproteins which locate within a 1.2 Mb cluster on the long arm of chromosome 19).

	In human, 11 different CEACAM1 splice variants have been reported. The domain structure of each protein isoform is illustrated as open box. N; N-terminal immunoglobulin variable-region-like (IgV-like) domain, A or B; subsets of constant-region-type-2-like (IgC2-like) domains, TM; transmembrane domain, C; cytoplasmic domain. Nomenclature number after CEACAM1 indicates the number of extracellular immunoglobulin-like domains, whereas the letter that follows this indicates the presence of either a long (L) or a short (S) cytoplasmic tail, a unique termini (C), or an Alu family repeat sequence present within the open reading frame (A). For example, CEACAM1 with four extracellular immunoglobulin-like domains and with a long cytoplasmic domain is called as CEACAM1-4L. The most common isoforms expressed by human immune cells are CEACAM1-4L, CEACAM1-3L, CEACAM1-4S and CEACAM1-3S.
Description	CEACAM1 is a single-pass type-1 glycoprotein which belongs within the Ig gene superfamily. It contains a 34 amino acid (aa) leader sequence, an extracellular domain which contains a N-terminal IgV-like domain and three of IgC2-like domains (382 aa), a transmembrane domain (43 aa), a cytoplasmic domain (67 aa) and two of the potential tyrosine phosphorylation sites. CEACAM1 is heavily N-glycosylated with more than 60% of the mass contributed by N-linked glycans.
Localisation	CEACAM1 isoforms with transmembrane domain are mostly cell-membrane anchored, whereas those without transmembrane domain are secreted. They are mostly expressed in cells of epithelial and endothelial, lymphoid and myeloid cells.
Function	CEACAM1 is capable of homophilic with CEACAM1 or heterophilic adhesion with CEA and CEACAM6. Isoforms of CEACAM1 with a long cytoplasmic domain generally transmit inhibitory signals, whereas isoforms with a short cytoplasmic domain indicate a regulated interaction with the cytoskeleton. CEACAM1 has been implicated in various types of intercellular-adhesion and intracellular-signaling of cell survival, differentiation and growth in both normal and cancer cells as follows: (1) CEACAM1 inhibits proliferation of both epithelial cells and T lymphocytes by a contact-mediated mechanism. In monocytes, CEACAM1 regulates phosphatidylinositol 3-kinase (PI3K) and Akt-dependent survival signal and inhibits apoptosis. (2) CEACAM1 induces apoptosis of mature colonocytes and mammary epithelial cells, which is in part of a morphogenetic process in the formation of glandular lumen. (3) CEACAM1 has been demonstrated to stimulate cellular migration of blood vessel endothelial cells. (4) In granulocytes, CEACAM1 mediates the binding to endothelial E-selectin. (5) The involvement of CEACAM1 in carcinogenesis is complex. In some types of cancer cells such as colon cancer and hepatoma loss or reduced expression of CEACAM1 is frequently observed, thereby it has been regarded as a tumor suppressor. However, in other types, for example, thyroid cancer and gastric cancer, CEACAM1 is up-regulated. (6) CEACAM1 exerts angiogenic properties and is a major effecter of VEGF in the early vascular formation. Since CEACAM1 is mainly expressed in tumor microvessels but not in large blood vessels, it may be a target for the therapy of tumor angiogenesis. (7) Neisseria gonorrhea triggers expression of CEACAM1 on primary endothelial cells by activating the immediate early response transcription factor NF-kappaB. Neisseria gonorrhoeae colony opacity-associated (Opa) proteins bind to human CEACAM on host cells including T lymphocytes, and Opa binding to CEACAM1 suppresses the activation of CD4+ T cells in response to a variety of stimuli. (8) CEACAM1 regulates insulin clearance in the liver.
Homology	CEACAM1 is the human homolog of a cell adhesion molecule (CAM) of the rat designated Cell-CAM. Rattus norvegicus: 70.74 (n), 56.12(a) (Percentage Identity). Mus musculus: 72.3 (n), 58.25 (a).

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