|CD66c||CEACAM8 (carcinoembryonic antigen-related cell adhesion molecule 6), NCA (nonspecific cross-reacting antigen), NCA-50/90|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
|90 / 90|
|CD66c is expressed on granulocytes and epithelial cells. Products of 4 of the 7 functional carcinoembryonic antigen (CEA) family genes, CD66a-d, are known to be expressed by hematopoietic cells. Expression of these molecules on hematopoietic cells is generally restricted to the myeloid lineage. These molecules are present at low levels on resting mature granulocytes but expression increases rapidly following activation with inflammatory agonists, probably as a result of exocytosis from storage granules. CD66c is detected on some macrophages in tissue sections and on a variety of epithelia. Soluble forms of CD66c are present in plasma.|
|MOLECULAR FAMILY NAME: Belongs to the carcinoembryonic antigen gene family.|
CD66c is a single-pass GPI-anchored glycoprotein. It contains a 34 aa leader sequence, a 284 aa extracellular domain which contains 2 Ig-like C2-type domains and 1 Ig-like V-type domain which are linked to a 24 aa GPI-anchor. The extracellular portions of all CD66 molecules possess a N-terminal V-type Ig-like domain which, like members of the CD2 family, lacks the canonical inter-b -sheet disulfide, followed by a variable number of C2-type Ig-like domains. CD66c is heavily glycosylated with more than 60% of the mass contributed by N-linked glycans, and they bear sialylated Le x, sLe x, CD15s, structures. The CEA family belongs within the Ig gene superfamily.
CD66c is GPI-anchored but with no splice variants, however NCA50 and NCA90 are two gylcosylated variants.
CD66c is heavily and variably N-glycosylated with 12 potential N-glycosylation sites.
|CD66 molecules can mediate cell-cell adhesion by homotypic interactions and/or by heterotypic interactions with other CD66 molecules. CD66c exhibits both heterotypic and homotypic interactions whereas CD66b binds only heterotypically to CD66c and CD66e. The binding sites for these interactions lie within their N-terminal V-set IgSF domains. Carbohydrate structures on CD66c mediate binding to E. coli type 1 fimbriae and may be important in presenting sLe x-related ligands to the endothelial cell adhesion molecule CD66e. MAbs specific for the GPI-anchored molecules CD66c coprecipitate Lyn and Hck.|
LIGANDS AND MOLECULES ASSOCIATED WITH CD66c
|The function of CD66c, while unclear, is capable of homophilic and heterophilic adhesion, E-selectin and galectin binding, type 1 fimbriae binding and transmembrane signaling and is capable of activating neutrophils. Association with some Src family kinases in neutrophils and the involvement in the transmembrane signaling results in the activation of neutrophils possibly by regulating ther activity of CD11/CD18. Evidence of heterodimerization of CD66a-c molecules on the surface of neutrophils leads to concomitant clustering of the CD11b subunit of CD11b/CD18 (CR3) and the activation of the integrin leading to increased adherence of cells to fibronectin. CD66c may also function as a cell-surface mediator of cell-specific interactions. The ability of CD66 molecules to mediate cell-cell adhesion and their rapid upregulation following activation suggests that they may contribute to the interactions of activated granulocytes with each other or with the endothelial or epithelia. However, direct functional evidence for such a role is lacking. Crosslinking of CD66 molecules with antibodies can stimulate integrin-mediated neutrophil adhesion to endothelial cells, suggesting a possible signaling role. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD66c IN INTACT ANIMAL
CD66c has potential applications in the detection of sites of infection and inflammation. CD66c functions as a receptor for N. gonorrhea and N. meningtidis and recognizes some type 1 fimbriae of E.coli. Inhibition of CD66c increases apoptotic rate of colon cancer cells and inhibits metastatic tumor growth.
|The CEA family in humans and other mammals. |
The human CEA molecules are a family of closely related, IgSF domain-containing glycoproteins encoded by a dense cluster of at least 18 genes within ~1.2 Mb with a 65%-75% sequence identity. Based on sequence similarity and gene proximity this family can be divided into 2 subgroups, with a 80%-95% sequence identity within each subgroup. The CEA subgroup, >7 genes, encodes predominantly cell surface molecules, whereas the pregnancy-specific glycoprotein (PSG) subgroup, >11 genes, encodes secreted molecules. CEA and PSG subgroups have also been identified in the mouse and the rat. However, molecules within the subgroups show greater intraspecies, >80%, than interspecies, ~60% identity, making it impossible to identify species orthologues. Indeed orthologues may not exist since sequence analysis suggests that there has been independent and parallel evolution of the CEA and PSG subgroups following the divergence of rodents and humans.
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD66c: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD66c: No information.
CD66c may play an important role in sites of inflammation. The data are consistent with the hypothesis that CD66c plays a signaling role and regulates the adhesion activity of CD11/CD18 in neutrophils. While the details of the "activation signal" transmitted by CD66 antigens are not known, the finding of tyrosine kinase activity associated with CD66a, CD66b and CD66c suggests that these kinase activities may be involved in signal transduction via CD66 family members.
Database accession numbers
Revised June 25, 2008