CD166 ALCAM(activated leukocyte cell adhesion molecule)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Epithelial Cell
T Cell
Neuron
Epithelium
Monocyte
Fibroblast
Lymphocyte
Endothelial Cell
B Cell
Stem Cell
Spleen
Placenta
Brain
Prostate
Liver
Nervous system
Blastocyst
Hematopoietic Cell
Breast
100 / 100
105 / 105

Expression
CD166 is expressed on cortical and medullary thymic epithelial cells, neurons, activated T cells, B cells, monocytes, fibroblasts, endothelium, epithelium, primitive subsets of hematopoietic cells including pluripotent stem cells, blastocysts and endometrium.    Expression is on mesenchymal stem cells and  progenitor cells.  Expression is in the spleen, placenta, liver, in neurons in the brain.  There is restricted expression in tumor cell lines.  B cells are preferentially expressed in highly metastasizing melanoma cell lines colorectal, prostate, bladder and breast cancers.  The avian equivalent, BEN, is expressed on epithelial cells of the Bursa.  In the nervous system, CD166 is expressed on unmyelinated nerve fibers including sympathatic and parasympathetic nerve fibers.  The distribution of BEN is well-characterized on developing sensory and motor neurons.


Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene superfamily.

CD166 is a single-pass type-1 556 aa glycoprotein.  It contains a secretory signal sequence, an extracellular domain which contains 3 Ig-like C2-type domains, 2 Ig-like V-type domains and 9 potential N-linked glycosylation sites, a hydrophobic transmembrane spanning domain and a 32 aa cytoplasmic domain with no known motifs.  The N-terminal Ig domain is the binding site for both homophilic and CD166-CD6 interactions.  CD166 is anchored to the actin cytoskeleton via the cytoplasmic domain but the receptors involved in this interaction are unknown.  The soluble CD166 is produced by proteolytic cleavage of extracellular domains or by alternative splicing.

MOLECULAR MASS
Cell Type Unreduced Reduced
T cell lymphoma 100-105 kDa 100-105 kDa

POST-TRANSCRIPTIONAL MODIFICATION
 
The soluble CD166 is produced by proteolytic cleavage of extracellular domains or by alternative splicing.  A recently described soluble isoform produced by alternative splicing has the N-terminal Ig V-like domain only and retains the ligand binding capacity of CD166.


POST-TRANSLATIONAL MODIFICATION

CD166 contains 10 potential N-linked glycosylation sites.

Ligands
CD166 on thymic epithelial cells, via its N-terminal IgSF V-set domain, mediates homophilic binding to the membrane proximal scavenger receptor domain of CD6 on thymocytes.  CD166 displays homophilic binding and binds CD6.   A homophilic interaction has been described for the chicken orthologue. 

LIGANDS AND MOLECULES ASSOCIATED WITH CD166
Molecule Comment
CD6 ALCAM (CD166) in the human system was first characterized as a ligand for CD6
30-35 kD protein Immunoprecipitation results have shown human ALCAM (CD166) is sometime associated with a 30-35 kDa protein
CD166 (homophilic) Chicken ALCAM (CD166) [known as BEN/DM-GRASP/SC-1] was shown to act as a homophilic adhesion molecule in the nervous system
NgCAM Chicken ALCAM (CD166) [known as BEN/DM-GRASP/SC-1] was shown to bind to NgCAM



Function
CD166 is an activated leucocyte adhesion molecule that binds to CD6.  It has been found in the development of many organs as well as hematopoiesis, endothelial and epithelial linings and the central and peripheral nervous systems.  Murine studies suggest a role for CD166 in hematopoietic cell and endothelual cell differentiation and migration.  Blocking the interaction of CD166+ APCs and CD6+ T cells with soluble monomeric CD166 or CD6 in vitro was found to reduce antigen-specific T cell proliferation and IL-2 production.  This suggests the CD166-CD6 interaction enhances antigen-specific T cell responses during an immune response.  CD166 is involved in the interaction among neuronal cells or immune cells and is involved in neurite extension by neurons via heterophilic and homophilic interactions.  Through its interaction with CD166 in the thymus, CD6 may have a role in T cell development.  There may be a role in the binding of T and B cells to activated leukocytes as well as interactions between cells of the nervous system.  A role in axonal guidance is postulated based on inhibitory effects with mAbs.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD166 IN INTACT ANIMAL

Knockout mice have motor and retinal ganglion cell axons that fasciculate poorly and are occasionally misdirected and have retinal exvaginated or invaginated regions with photoreceptor ectopias similiar to those found in some human retinopathies.  CD166 is a marker used to select pluripotent stem cells from mesenchymal progenitor populations by flow cytometry.  Expression levels are used as a prognostic indicator for melanoma, bladder, prostate, colorectal and breast cancer.  Increased expression generally correlates with more aggressive disease and a poorer prognosis, with the exception of breast cancer, where decreased CD166 expression is indicative of tumor metastasis and poor prognosis.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD166: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD166: No information.

ADDITIONAL INSIGHTS

The relevance of interactions of CD166 with CD6 in the immune system remains to be demonstrated, especially with regards to whether or not they are involved in T cell activation and/or the cytokine production. However, it is intriguing to speculate that interactions between CD6+ T cells and cells in the nervous system could be involved in the pathologies observed in certain neurodegenerative diseases such as multiple sclerosis.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
ChickenP42292X64301
HumanEntrezgene 214Q13740
MouseL25274
Antibodies
3A6   View Reactivity

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University