• DRAP-27
• MRP-1
• p24

MAJOR LINKS FOR CD9  

• NCBI LocusLink Record: 928
• Mendelian Inheritance in Man (OMIM): 143030
• SwissProt annotated protein record: P21926

• CD9 upregulates HB-EGF activity as a receptor for diphtheria toxin as well as its juxtacrine activity

CELLULAR FUNCTION OF CD9  

• CD9 mAbs modulate cell adhesion and migration
• CD9 mAbs trigger platelet activation 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 costimulatory activity for T cells

DISEASE RELEVANCE OF CD9 AND FUNCTION OF CD9 IN INTACT ANIMAL  

• CD9 mAbs inhibit infection by FIV and CDV (canine distemper virus) 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 actuarial survival in lung cancer Higashiyama et al. Cancer Research 55: 6040-6044 1995**
• Transfection of CD9 in murine melanoma cells has been shown to reduce metastasis

• Families in which CD9 is a member
  • CD9-->TM4SF

MOLECULAR STRUCTURE OF CD9  

• 228 amino acids
• CD9 is a type III membrane protein, with four putative transmembrane domains, delimiting two unequal extracellular loops
• The short ends are located in the cytoplasm
• A signature of the tetraspan superfamily is present between transmembrane regions II and III: G-x(3)-[LIVMF]-x(2)-[GSA]-[LIVMF](2)-G-C-x-[GA]-[STA]-x(2)-[EG]-x(2)-[CW]-[LIVM](2)

MOLECULAR MASS OF CD9  

POST-TRANSCRIPTIONAL MODIFICATION OF CD9   - No information

POST-TRANSLATIONAL MODIFICATION OF CD9  

• Both the 24 and 26 kDa forms of CD9 are acylated
• Both the 24 and 26 kDa forms of CD9 are O-glycosylated
• The 26 kDa form appears to be N-glycosylated
• There is only one N-glycosylation site and it is located within the shorter extracellular region*

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

SUBSTRATES FOR CD9   - No information

ENZYMES WHICH MODIFY CD9   - No information

LIGANDS FOR CD9 AND MOLECULES ASSOCIATED WITH CD9  

• Multiple tetraspans, integrins and MHC class II (e.g. HLA-DR) may be present in one large complex

• Platelets
• Early B cells
• Activated and differentiating B cells (Yashukawa et al. 1988, Zola et al. 1991, 1989)**
• Activated T cells
• Eosinophils
• Basophils
• Endothelial cells
• Brain and peripheral nerves
• Vascular smooth muscle, and cardiac muscle
• Epithelia
• It is often described as expressed by monocytes but this expression is likely to result from sticking platelet fragments

• 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
• The exact function of these molecules remains unknown. They have been suggested to form ion channels, or to participate in membrane "organization"*

SELECTION OF OTHER CD9-SPECIFIC REFERENCE MAB  

REVIEWS

1. Rubinstein E,Boucheix C,Worthington RE,Carroll RC Anti-platelet antibody interactions with Fc gamma receptor. Semin Thromb Hemost 1995 21:10 PubMed

2. Wright MD,Tomlinson MG The ins and outs of the transmembrane 4 superfamily. Immunol Today 1994 15:588 PubMed

PRIMARY CITATIONS

3. Berditchevski F,Zutter MM,Hemler ME Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Mol Biol Cell 1996 7:193 PubMed

4. Boucheix C,Benoit P,Frachet P,Billard M,Worthington RE,Gagnon J,Uzan G Molecular cloning of the CD9 antigen. A new family of cell surface proteins. J Biol Chem 1991 266:117 PubMed

5. Ikeyama S,Koyama M,Yamaoko M,Sasada R,Miyake M Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA. J Exp Med 1993 177:1231 PubMed

6. Iwamoto R,Higashiyama S,Mitamura T,Taniguchi N,Klagsbrun M,Mekada E Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J 1994 13:2322 PubMed

7. Lanza F,Wolf D,Fox CF,Kieffer N,Seyer JM,Fried VA,Coughlin SR,Phillips DR,Jennings LK cDNA cloning and expression of platelet p24/CD9. Evidence for a new family of multiple membrane-spanning proteins. J Biol Chem 1991 266:10638 PubMed

8. Le Naour F,Prenant M,Francastel C,Rubinstein E,Uzan G,Boucheix C Transcriptional regulation of the human CD9 gene: characterization of the 5'-flanking region. Oncogene 1996 13:481 PubMed

9. Loffler S,Lottspeich F,Lanza F,Azorsa DO,ter Meulen V,Schneider-Schaulies J CD9, a tetraspan transmembrane protein, renders cells susceptible to canine distemper virus. J Virol 1997 71:42 PubMed

10. Oritani K,Wu X,Medina K,Hudson J,Miyake K,Gimble JM,Burstein SA,Kincade PW Antibody ligation of CD9 modifies production of myeloid cells in long- term cultures. Blood 1996 87:2252 PubMed

11. Rubinstein E,Le Naour F,Billard M,Prenant M,Boucheix C CD9 antigen is an accessory subunit of the VLA integrin complexes. Eur J Immunol 1994 24:3005 PubMed

12. Rubinstein E,Le Naour F,Lagaudriere-Gesbert C,Billard M,Conjeaud H,Boucheix C CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol 1996 26:2657 PubMed

13. Seehafer JG,Tang SC,Slupsky JR,Shaw AR The functional glycoprotein CD9 is variably acylated: localization of the variably acylated region to a membrane-associated peptide containing the binding site for the agonistic monoclonal antibody 50H.19. Biochim Biophys Acta 1988 957:399 PubMed

14. Shaw AR,Domanska A,Mak A,Gilchrist A,Dobler K,Visser L,Poppema S,Fliegel L,Letarte M,Willett BJ Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation. J Biol Chem 1995 270:24092 PubMed

15. Tai XG,Yashiro Y,Abe R,Toyooka K,Wood CR,Morris J,Long A,Ono S,Kobayashi M,Hamaoka T,Neben S,Fujiwara H A role for CD9 molecules in T cell activation. J Exp Med 1996 184:753 PubMed

16. Willett BJ,Hosie MJ,Jarrett O,Neil JC Identification of a putative cellular receptor for feline immunodeficiency virus as the feline homologue of CD9. Immunology 1994 81:228 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov