EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily

J Biol Chem. 2001 Nov 2;276(44):40545-54. doi: 10.1074/jbc.M107338200. Epub 2001 Aug 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / metabolism*
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Immunoglobulins / chemistry*
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism
  • Membrane Glycoproteins*
  • Membrane Proteins*
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Tetraspanin 28
  • Tetraspanin 29
  • Tumor Cells, Cultured


  • Antigens, CD
  • CD81 protein, human
  • CD9 protein, human
  • DNA Primers
  • IGSF8 protein, human
  • Immunoglobulins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Tetraspanin 28
  • Tetraspanin 29

Associated data

  • GENBANK/AF407247