CD106 VCAM-1 (vascular cell adhesion molecule-1), INCAM-110
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelium
Follicular Cell
Dendritic Cell
Macrophage
Bone Marrow
Stromal Cell
Endothelial Cell
Kidney
Skeletal muscle
Placenta
Heart
Brain
Cytokine
100 / 100
110 / 110

Expression
CD106 is expressed predominantly on vascular endothelium but has also been identified on follicular and interfollicular dendritic cells, some macrophages, bone marrow stromal cells, and non-vascular cell populations within joints, kidney, muscle, heart, placenta and brain.  Expression on endothelial cells as well as many other cells is induced by inflammatory stimuli and cytokines.  Activated endothelial cells can release soluble forms of CD106 which can be detected in the blood.

Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin supergene family.

CD106 is a single-chain type-1 sialoglycoprotein.  It contains an extracellular domain which contains 7 Ig-like C2-type domains, a transmembrane and a cytoplasmic domain.  The extracellular domains 1-3 show substantial sequence similarity to domains 4-5, which is consistent with an internal duplication event during evolution.  The structures of domains 1 and 2 have been determined by X-ray crystallography.  As a result domain 1 was classified as an 1-type IgSF domain on structural grounds.  The domains 1+2 and 4+5 fragments are closely related to the 2 IgSF domains of MAdCAM-1, (which also binds the integrin a4b7) as well as domains 1 and 2 of the CD18 binding molecules CD50, CD54 and CD102. 
CD106 encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium.  Alternative splicing can produce a 6 IgSF domain form lacking domain 4 or, in the mouse, a GPI-anchored form of CD106 comprising domains 1-3.  The structures of domains 1 and 2 have been determined by X-ray crystallography.    The membrane-distal domains of all these molecules have atypical disulfides between the B-C and F-G loops as well as an I/L D/E S/TxL motif in the C-D loop, which forms part of the integrin binding site.  CD106 is highly conserved between humans and rodents with an ~76% overall, and a 100% within the cytoplasmic domain).

MOLECULAR MASS
Cell Type Unreduced Reduced
100 - 110 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms, one of which had 6 Ig-like C2-type domains. 

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
CD106 binds the integrins a4b1 (CD49d/CD29, VLA-4) and a4b7.  CD49d/CD29 is the dominant ligand in cells expressing both integrins.  CD106 has 2 independent binding sites for VLA-4 in domains 1 and 4, respectively. Both sites lie on the GFC b -sheets of these domains and include the conserved C-D loop motif IDSPL.

Function
CD106 contributes to leukocyte adhesion, transmigration and co-stimulation of T cell proliferation.  It is a receptor for the VLA-4 integrin which is a homing receptor for lymphocytes.  Endothelial CD106 contributes to the extravasation of lymphocytes, monocytes, basophils and eosinophils but not neutrophils from blood vessels, particularly at sites of inflammation.  Unlike the b integrins, the CD106/VLA-4 interaction can mediate both the initial tethering and rolling of lymphocytes on endothlium as well as their subsequent arrest and firm adhesion.  CD106 expressed in non-vascular tissues has been implicated in the interaction of hematopoietic progenitors with bone marrow stromal cells, B cell binding to follicular dendritic cells, co-stimulation of T cells, and embryonic development. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD106 IN INTACT ANIMAL: 

CD106 mediates leukocyte-endothelial cell adhesion and signal transduction and may play a role in the development of artherosclerosis and rheumatoid arthritis.  It also binds specific blood leukocytes and tumor cells.  Mice deficient in CD106 have defects in the development of the placenta and heart and die during embryogenesis.  These mice have severe organogenesis defects and die as embryos.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD106: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD106: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7412P19320
MouseJN0581P29533M84487
RatJS0675P29534M84488
Antibodies
1.G11B1   View Reactivity

Revised June 25, 2008


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