CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities

Int Immunol. 2003 Mar;15(3):313-29. doi: 10.1093/intimm/dxg032.


Interaction trap cloning was used to identify a CD2 cytoplasmic tail-binding protein termed CD2BP3. CD2BP3 is the major RNA splice variant of the CIN85 locus in human T lymphocytes, lacking SH3A, the first of three SH3 domains found in CIN85, but retaining SH3B, SH3C, a proline-rich domain and C-terminal coiled coil. CD2BP3 has 35% amino acid identity to CMS, a structurally related protein binding to the same highly conserved segment of the CD2 tail and known to be involved in T cell polarization/cytoskeletal interactions. Unlike CMS, however, CD2BP3 does not co-localize with F-actin and binds p130(Cas) weakly, if at all. Moreover, CIN85/CD2BP3 proteins are readily degraded by TCR cross-linking, consistent with the presence of a PEST sequence C-terminal to SH3C. CIN85 SH3A and CIN85/CD2BP3 SH3B bind to proline-rich segments within CIN85/CD2BP3 themselves as evidenced by mAb accessibility analysis and protein interaction studies including c-Cbl binding. This form of intramolecular regulation is not manifest by CMS. CMS and CIN85 activities are antagonistic, while the functions of CIN85 and CD2BP3 are also distinct. Thus, CD2-mediated adhesion, signaling and cell motility are regulated in a highly complex manner.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • CD2 Antigens / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Crk-Associated Substrate Protein
  • Cytoskeletal Proteins*
  • Cytoskeleton / metabolism
  • Humans
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Proteins*
  • Retinoblastoma-Like Protein p130
  • Sequence Alignment
  • Sequence Analysis, Protein
  • T-Lymphocytes / metabolism*
  • Two-Hybrid System Techniques


  • Adaptor Proteins, Signal Transducing
  • BCAR1 protein, human
  • CD2 Antigens
  • CD2-associated protein
  • Carrier Proteins
  • Crk-Associated Substrate Protein
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Proteins
  • Retinoblastoma-Like Protein p130
  • SH3KBP1 protein, human