CD9 Tspan-29 (tetraspanin-29), MRP-1 (motility-related prottein-1, leukocyte antigen MIC3, p24, DRAP27 (monkey)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 4 span
Platelet
Brain
Epithelia
Macrophage
Granulocyte
Monocyte
B Cell
T Cell
Basophil
Endothelial Cell
Muscle, Smooth
Muscle. Cardiac
Nerve Cell
Eosinophil
24 / 24
26 / 26

Expression
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.


Structure
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.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
All cell types 24 kDa (major band)
26 kDa (minor band)
Increased on differentiating B cells

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

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
LIGANDS AND MOLECULES ASSOCIATED WITH CD9
Molecule Comment
CD63 CD9 associates with other members of the tetraspan superfamily (CD63, CD81, CD82)
CD81 CD9 associates with other members of the tetraspan superfamily (CD63, CD81, CD82)
CD82 CD9 associates with other members of the tetraspan superfamily (CD63, CD81, CD82)
b-1 integrins In various cell line
CD41/CD61 (gpIIb/IIIa) Associates with CD9 in platelets
HLA-DR In pre-B cells and transfected B cell lines
HB-EGF (heparin-binding EGF) CD9 is also associated with the transmembrane precursor form of a growth factor, HB-EGF (heparin-binding EGF)
P14 kinase CD9 is associated with P14

Multiple tetraspans, integrins and MHC class II like HLA-DR may be present in 1 large complex.




Function
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.

BIOCHEMICAL ACTIVITY

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.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD9
Molecule Comment
SP1 SP1 has been shown to bind to the CD9 promoter

Another, presumably new, transcription factor may also participate in the regulation of expression of CD9.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD9: No information.

ADDITIONAL INSIGHTS

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
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 928P21926
MouseP40240L08115
RatS39262P40241X76489
Antibodies
B18A   View Reactivity
BAQ86A   View Reactivity
LT86A   View Reactivity
ML13   View Reactivity
MM2/57   View Reactivity
P1/33/2   View Reactivity
RH1A   View Reactivity
TH2   View Reactivity
vpg15   View Reactivity

Revised June 25, 2008


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