title: EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily.
abstract: A novel Ig superfamily protein, EWI-2, was co-purified with tetraspanin protein CD81 under relatively stringent Brij 96 detergent conditions and identified by mass spectrometric protein sequencing. EWI-2 associated specifically with CD9 and CD81 but not with other tetraspanins or with integrins. Immunodepletion experiments indicated that EWI-2-CD9/CD81 interactions are highly stoichiometric, with approximately 70% of CD9 and CD81 associated with EWI-2 in an embryonic kidney cell line. The EWI-2 molecule was covalently cross-linked (in separate complexes) to both CD81 and CD9, suggesting that association is direct. EWI-2 is part of a novel Ig subfamily that includes EWI-F (F2alpha receptor regulatory protein (FPRP), CD9P-1), EWI-3 (IgSF3), and EWI-101 (CD101). All four members of this Ig subfamily contain a Glu-Trp-Ile (EWI) motif not seen in other Ig proteins. As shown previously, the EWI-F molecule likewise forms highly proximal, specific, and stoichiometric complexes with CD9 and CD81. Human and murine EWI-2 protein sequences are 91% identical, and transcripts in the two species are expressed in virtually every tissue tested. Thus, EWI-2 potentially contributes to a variety of CD9 and CD81 functions seen in different cell and tissue types.
authors.affiliation: Dana-Farber Cancer Institute and the Department of Pathology, Harvard Medical School, Boston, Mssachusetts 02115, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Stipp
authors.forename: T V
authors.initials: TV
authors.lastname: Kolesnikova
authors.forename: M E
authors.initials: ME
authors.lastname: Hemler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; C554798:CD81 protein, human; C554869:CD9 protein, human; D017931:DNA Primers; C440028:IGSF8 protein, human; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29