Schematic model of CD9 and proposed functional domains.

Amino acid sequence determination and antibody-binding studies suggest that CD9 consists of 2 EC loops, EC1 and EC2, and 4 TM domains (TM1-TM4), with the N and C termini located intracellularly.1 EC2 aa119-138 has been identified as the binding site for HB-EGF39; aa168-185 as a key region for CD9-FN binding; aa144-185 competes for mAb7 binding to intact CD9; aa169-180 has been identified to play a role in regulating cell motility25; and aa 173-192 affects CHO cell adhesion and pericellular FN matrix assembly and encompasses a corresponding region on CD151 that has been reported to facilitate TM4SF-integrin association (aa182-217).42 Preliminary data suggest that EC1^35–58 in conjunction with EC2^113–133modulates cell spreading. EC1 appears critical for CD9 effects on cell proliferation and cell survival (Bao et al, manuscript submitted).