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Gene Review

SH3BP2  -  SH3-domain binding protein 2

Homo sapiens

Synonyms: 3BP-2, 3BP2, CRBM, CRPM, RES4-23, ...
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Disease relevance of SH3BP2

  • Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism [1].
  • Here we show that 3BP2 is tyrosine phosphorylated following BCR aggregation on B lymphoma cells, and that 3BP2 is a substrate for Syk and Fyn, but not Btk [2].

High impact information on SH3BP2

  • Mutations in the SH3-domain binding protein 2 (SH3BP2) are known to cause a rare childhood disorder called cherubism that is characterized by inflammation and bone loss in the jaw, but the mechanism has remained unclear [3].
  • Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism [1].
  • Thus, 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription [4].
  • Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation [4].
  • 3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells, including in antigen receptor-stimulated T cells [4].

Chemical compound and disease context of SH3BP2


Biological context of SH3BP2


Anatomical context of SH3BP2

  • Furthermore, overexpression and RNAi blocking experiments showed that 3BP2 regulated BCR-mediated activation of nuclear factor of activated T cells (NFATs) [2].
  • To further explore the function of 3BP2 in B cells, we screened a yeast 2-hybrid B-lymphocyte library and found 3BP2 as a binding partner of Vav proteins [2].
  • To examine the role of 3BP2 in mast cells, we overexpressed the SH2 domain of 3BP2 in the RBL-2H3 cells [8].
  • CD244-3BP2 interaction was direct and regulated by phosphorylation, as shown by a three-hybrid analysis in yeast and NK cells [9].
  • The adapter 3BP2: how it plugs into leukocyte signaling [10].

Associations of SH3BP2 with chemical compounds

  • Tyrosine phosphorylation of adaptor protein 3BP2 induces T cell receptor-mediated activation of transcription factor [11].
  • Although mutation of Tyr337 to phenylalanine abrogated human 3BP2 binding, we still observed SAP association, indicating that this motif is not essential for SAP recruitment [9].
  • In addition, proline-rich region of 3BP2 bound to the Lyn-SH3 domain [12].
  • We identified residues Ser(225) and Ser(277) of 3BP2 as being essential for interaction with 14-3-3 family proteins, optimal 3BP2 serine phosphorylation, and then for 3BP2-dependent function [13].

Physical interactions of SH3BP2


Regulatory relationships of SH3BP2


Other interactions of SH3BP2

  • 3BP2 also interacted with other components of the BCR signaling pathway, including Syk and phospholipase C gamma (PLC-gamma) [2].
  • This suggests the presence of an intermediate molecule between activated CR2 and tyrosine-phosphorylated p95, which may be 3BP2 [17].
  • When binding to variant phosphopeptides based on this membrane-distal tyrosine was tested, altering the amino acids immediately following the phosphotyrosine could selectively abolish the interaction with Shc or Grb2, or the binding to both Grb2 and 3BP2 [18].
  • Tyr337 on CD244, part of a consensus motif for SAP/SH2 domain protein 1A binding, was critical for the 3BP2 interaction [9].
  • We previously showed that the cytoplasmic adapter 3BP2 (also known as SH3BP2) promotes NFAT/AP-1 transcriptional activities in T cells through the activation of Ras- and calcineurin-dependent pathways [13].

Analytical, diagnostic and therapeutic context of SH3BP2


  1. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Ueki, Y., Tiziani, V., Santanna, C., Fukai, N., Maulik, C., Garfinkle, J., Ninomiya, C., doAmaral, C., Peters, H., Habal, M., Rhee-Morris, L., Doss, J.B., Kreiborg, S., Olsen, B.R., Reichenberger, E. Nat. Genet. (2001) [Pubmed]
  2. The adaptor protein 3BP2 associates with VAV guanine nucleotide exchange factors to regulate NFAT activation by the B-cell antigen receptor. Foucault, I., Le Bras, S., Charvet, C., Moon, C., Altman, A., Deckert, M. Blood (2005) [Pubmed]
  3. Jawing about TNF: New Hope for Cherubism. Novack, D.V., Faccio, R. Cell (2007) [Pubmed]
  4. Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation. Deckert, M., Tartare-Deckert, S., Hernandez, J., Rottapel, R., Altman, A. Immunity (1998) [Pubmed]
  5. Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation. Lietman, S.A., Kalinchinko, N., Deng, X., Kohanski, R., Levine, M.A. Hum. Mutat. (2006) [Pubmed]
  6. Identification and characterization of the human homologue of SH3BP2, an SH3 binding domain protein within a common region of deletion at 4p16.3 involved in bladder cancer. Bell, S.M., Shaw, M., Jou, Y.S., Myers, R.M., Knowles, M.A. Genomics (1997) [Pubmed]
  7. A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism. Imai, Y., Kanno, K., Moriya, T., Kayano, S., Seino, H., Matsubara, Y., Yamada, A. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. (2003) [Pubmed]
  8. Regulation of FcepsilonRI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells. Sada, K., Miah, S.M., Maeno, K., Kyo, S., Qu, X., Yamamura, H. Blood (2002) [Pubmed]
  9. The adaptor protein 3BP2 binds human CD244 and links this receptor to Vav signaling, ERK activation, and NK cell killing. Saborit-Villarroya, I., Del Valle, J.M., Romero, X., Esplugues, E., Lauzurica, P., Engel, P., Martín, M. J. Immunol. (2005) [Pubmed]
  10. The adapter 3BP2: how it plugs into leukocyte signaling. Deckert, M., Rottapel, R. Adv. Exp. Med. Biol. (2006) [Pubmed]
  11. Tyrosine phosphorylation of adaptor protein 3BP2 induces T cell receptor-mediated activation of transcription factor. Qu, X., Kawauchi-Kamata, K., Miah, S.M., Hatani, T., Yamamura, H., Sada, K. Biochemistry (2005) [Pubmed]
  12. Adaptor protein 3BP2 is a potential ligand of Src homology 2 and 3 domains of Lyn protein-tyrosine kinase. Maeno, K., Sada, K., Kyo, S., Miah, S.M., Kawauchi-Kamata, K., Qu, X., Shi, Y., Yamamura, H. J. Biol. Chem. (2003) [Pubmed]
  13. The chaperone protein 14-3-3 interacts with 3BP2/SH3BP2 and regulates its adapter function. Foucault, I., Liu, Y.C., Bernard, A., Deckert, M. J. Biol. Chem. (2003) [Pubmed]
  14. Regulation of NK cell-mediated cytotoxicity by the adaptor protein 3BP2. Jevremovic, D., Billadeau, D.D., Schoon, R.A., Dick, C.J., Leibson, P.J. J. Immunol. (2001) [Pubmed]
  15. High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides. Musacchio, A., Saraste, M., Wilmanns, M. Nat. Struct. Biol. (1994) [Pubmed]
  16. Cherubism - new hypotheses on pathogenesis and therapeutic consequences. Hyckel, P., Berndt, A., Schleier, P., Clement, J.H., Beensen, V., Peters, H., Kosmehl, H. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. (2005) [Pubmed]
  17. Signaling through the EBV/C3d receptor (CR2, CD21) in human B lymphocytes: activation of phosphatidylinositol 3-kinase via a CD19-independent pathway. Bouillie, S., Barel, M., Frade, R. J. Immunol. (1999) [Pubmed]
  18. Contribution of the membrane-distal tyrosine in intracellular signaling by the granulocyte colony-stimulating factor receptor. Kendrick, T.S., Lipscombe, R.J., Rausch, O., Nicholson, S.E., Layton, J.E., Goldie-Cregan, L.C., Bogoyevitch, M.A. J. Biol. Chem. (2004) [Pubmed]
  19. Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Lo, B., Faiyaz-Ul-Haque, M., Kennedy, S., Aviv, R., Tsui, L.C., Teebi, A.S. Am. J. Med. Genet. A (2003) [Pubmed]
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