CD66d CEACAM3 (carcinoembryonic antigen-related cell adhesion molecule), CGM1
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Granulocyte
Hematopoietic Cell
Epithelia
Myeloid Cell
35 / 35

Expression
CD66d is expressed on granulocytes.  Products of 4 of the 7 functional carcinoembryonic antigen (CEA) family genes, CD66a-d, are known to be expressed on 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.  CD66d is detected on some macrophages in tissue sections.  CD66d is also expressed on a variety of epithelia..


Structure
MOLECULAR FAMILY NAME: Belongs to the carcinoembryonic antigen gene family.

CD66d is a single-pass type-1 glycoprotein. It contains a 34 aa leader peptide, an 108 aa N-terminal extracellular domain which contains an Ig-like V-type domain, a 39 aa transmembrane domain, a 71 aa cytoplasmic domain containing 2 YXXL motifs. The extracellular portions of all CD66 molecules possess the 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-set IgSF domains.  The YxxL/M motifs resemble conventional ITAM-like motifs YxxLx7YxxM.  The CEA gene family belongs within the Ig gene superfamily.  In contrast to some members of the CEA family, which are GPI-anchored, the CD66d molecules is a transmembrane glycoprotein.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Granulocytes 35 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms, 1 of which alters the reading frame leading to the loss of YXXL motifs.

POST-TRANSLATIONAL MODIFICATION

CD66d is heavily and variably N-glycosylated with 2 N-glycosylation sites and has 2 potential phosphorylation sites in the cytoplasmic domain.


Ligands
CD66 molecules can mediate cell-cell adhesion by homotypic interactions and/or by heterotypic interactions with other CD66 molecules.

LIGANDS AND MOLECULES ASSOCIATED WITH CD66d
Molecule Comment
None known No homotypic or heterotypic adhesion has been identified.




Function
CD66d may be involved in signaling and adhesion and is capable of activating neutrophils.  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 endothelia 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 CD66d IN INTACT ANIMAL

CD66d functions as a receptor for N. gonorrhea and N. meningitidis.  Interaction of CD66d with Opa proteins of pathogenic Neisseria results in signaling via Src family kinases and efficient uptake of the organism.  Less-efficient CD66d mediated uptake of N.gonorrhoea has also been observed in the absence of tyrosine phosphorylation.  CD66d is used by several human bacterial pathogens, including Neisseria, Moraxella and Hemophilus species, to anchor themselves to and/or invade host cells.


Comments
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 CD66d: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD66d: No information.

ADDITIONAL INSIGHTS

CD66d may play a signaling role and regulates the adhesion activity of CD11/CD18 in neutrophils.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 1084P40198
Antibodies
YTH71.3   View Reactivity

Revised June 25, 2008


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