|CD9||Tspan-29 (tetraspanin-29), MRP-1 (motility-related prottein-1, leukocyte antigen MIC3, p24, DRAP27 (monkey)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 3 glycoprotein, 4 span
|24 / 24|
26 / 26
|CD9 is expressed on platelets, early B cells, activated and differentiating B cells, activated T cells, and at lower levels in eosinophils, granulocytes, monocytes, and macrophages. Expression is on basophils, endothelial cells, brain and peripheral nerves, vascular smooth muscle, cardiac muscle, and epithelia. CD9 is often described as expressed by monocytes but this expression is likely to result from adherent fragments from platelets.|
|MOLECULAR FAMILY NAME: Belongs to the transmembrane 4 superfamily.|
CD9 is a multi-pass type-3 4 span 228 aa glycoprotein. It contains 2 unequal extracellular domains, 4 transmembrane domains containing a signature sequence common to tetraspan family members between domains 2 and 3 and a short cytoplasmic domain containing N- and C-termini. CD9 is highly conserved amongst vertebrates, the human CD9 protein sharing 65% and 59% sequence identity with the shark and hagfish CD9 orthologues, respectively.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
Both the 24kDa and 26 kDa forms of CD9 are acylated and are O-glycosylated. The 26 kDa form appears to be N-glycosylated. There is only 1 N-glycosylation site and it is located within the shorter extracellular region.
| LIGANDS AND MOLECULES ASSOCIATED WITH CD9|
Multiple tetraspans, integrins and MHC class II like HLA-DR may be present in 1 large complex.
|CD9 mediates signal transduction events that play a role in the regulation of cell development, activation, growth and motility. CD9 can modulate cell adhesion and migration and triggers platelet activation and aggregation in association with CD41/CD61 but this is blocked by mAbs directed to the platelet Fc receptor CD32. In mice, CD9 mAb KMC8.8 has been shown to inhibit the production of myeloid cells in vitro. In mice, CD9 mAb 9D3 has a co-stimulatory activity for T cells. CD9 mAbs promote pre-B cell adhesion in vitro via the integrins CD29/CD49d VLA-4 and CD29/CD49e VLA-5. Studies using CD9-transfected cells showed that CD29 b1 integrin-dependent motility of a B cell line was enhanced by CD29 expression and was dependent on protein tyrosine kinases. Another study showed that tumor cell motility and metastasis were suppressed by CD9 expression. CD9 mAbs are potent activators of platelet aggregation and induce activation of the non-receptor protein tyrosine kinase Syk. In mouse T cells, a CD9 mAb has been shown to deliver a potent co-stimulatory signal.|
CD9 upregulates HB-EGF activity as a receptor for diphtheria toxin as well as its juxtacrine activity.
DISEASE RELEVANCE AND FUNCTION OF CD9 IN INTACT ANIMAL
CD9 appears to promote muscle cell fusion and supports myotube maintenance. CD9 mAbs inhibit infection by feline immunodeficiency virus (FIV) and canine distemper virus (CDV) but CD9 does not directly bind the virus, suggesting a role as a viral co-receptor, as for diphtheria toxin. CD9 mAbs have been used for immunophenotyping leukemias and bone marrow purging in autologous bone marrow transplantation. The expression of CD9 is inversely correlated with metastasis in melanoma and breast cancer. CD9 expression is inversely correlated with actual survival in lung cancer. Transfection of CD9 in murine melanoma cells has been shown to reduce metastasis. Knockout mice show severe reduction in female fertility.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD9
Another, presumably new, transcription factor may also participate in the regulation of expression of CD9.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD9: No information.
The tetraspans may participate in large molecular complexes. It is likely that the effects of tetraspans mAb are triggered through associated molecules. It has, however, not been definitively demonstrated and the exact function of these molecules remains unknown. They have been suggested to form ion channels, or to participate in membrane "organization".
Database accession numbers
Revised June 25, 2008