CD66b CEACAM8 ( carcinoembryonic antigen-related cell adhesion molecule 8), CGM6, NCA-95, previously CD67
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Granulocyte
Hematopoietic Cell
Myeloid Cell
Bone Marrow
Leukocyte
Leukemia, Myeloid
Plasma
95 / 95
100 / 100

Expression
CD66b, formerly was CD67, is expressed on granulocytes.  Expression is in leukocytes of chronic meyloid leukemia patients and bone marrow.  Products of 4 of the 7 functional carcinoembryonic antigen (CEA) family genes, CD66a-d, are known to be expressed on hematopoietic cells.  Expression of molecules on hematopoietic cells is generally restricted to the myeloid lineage, particularly in the case of CD66b.  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.  Soluble forms of CD66b are present in plasma.

 

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

CD66b is a single-pass GPI-anchored glycoprotein.  It contains a 34 aa leader sequence, a 284 aa extracellular which contains N-terminal Ig-like V-type domain and 2 Ig-like C2-type domains and followed by a 29 aa hydrophobic domain that is anchored to the membrane by GPI.   The extracellular portions of all CD66 molecules possess a N-terminal V-set Ig domain which, like members of the CD2 family, lacks the canonical inter-b -sheet disulfide, followed by a variable number of C2-set Ig domains.  CD66b is heavily glycosylated with more than 60% of the mass contributed by N-linked glycans, and they bear sialylated L3 x, sLe x, CD15s, structures.  The CEA family belongs within the Ig gene superfamilty.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Granulocytes 95-100 kDa

POST-TRANSCRIPTIONAL MODIFICATION

CD66b is GPI-anchored with no splice variants.

POST-TRANSLATIONAL MODIFICATION

CD66b is heavily and variably N-glycosylated with 11 N-glycosylation sites.

Ligands
CD66 molecules can mediate cell-cell adhesion by homotypic interactions and/or by heterotypic interactions with other CD66 molecules.  CD66b binds only heterotypically to CD66c and CD66e.  The bindings sites for these interactions lie within their N-terminal V-set Ig domains.  MAbs specific for the GPI-anchored molecules CD66b coprecipitate Lyn and Hck.

LIGANDS AND MOLECULES ASSOCIATED WITH CD66b
Molecule Comment
CD66c CD66b binds the protein core of CD66c not the carbohydrate
Src family kinases Some Src family kinases associate with CD66b in neutrophils




Function
CD66b is capable of heterophilic adhesion by binding the protein core of CD66c.  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.  Anti-CD66b mAbs augment the respiratory burst activity of neutrophils, and the binding of anti-CD66b mAbs increases upon granulocyte activation, apparently due to mobilization of an intracellular pool of the antigen.  CD66b associates with some Src family kinases in neutrophils and is involved in transmembrane signaling which results in activation of neutrophils possibly by regulating activity of CD11/CD18.  Upon activation of neutrophils, CD66b is shed, however, no function has as yet been attributed to the soluble protein.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD66b IN INTACT ANIMAL

CD66b has a potential application in the detecting sites of infection and inflammation.

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 CD66b: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD66b: No information.

ADDITIONAL INSIGHTS

CD66b exhibits only heterotypic adhesion with CD66c with no homophilic activity, suggesting the possibility that CD66b plays a role in the interaction between granulocytes or between granulocytes and epithelial cells. The data are consistent with the hypothesis that CD66b 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. CD66b is released during granulocyte activation, leading in vitro and in vivo to soluble protein with unknown function.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 1088P31997
Antibodies
G10F5   View Reactivity

Revised June 25, 2008


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