Member database | CATH-Gene3D |
CATH-Gene3D type | homologous superfamily |
Description Imported from IPR036481
This entry represents the oligomerisation domain of the breakpoint cluster region oncoprotein Bcr, and the Bcr/Abl (Abelson-leukemia-virus) fusion protein created by a reciprocal (9;22) fusion
[3]. Brc displays serine/threonine protein kinase activity (
2.7.11.1), acting as a GTPase-activating protein for RAC1 and CDC42. Brc promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them
[2]. The Bcr/Abl fusion protein loses some of the regulatory function of Bcr with regards to small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells
[3].
The Bcr, Bcr/Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (α1), a flexible loop and a long C-terminal helix (α2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the α2 helices and domain swapping of two α1 helices, where one α1 helix swings back and packs against the α2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerization domain is essential for the oncogenicity of the Bcr-Abl protein
[1].
References Imported from IPR036481
1.Structure of the Bcr-Abl oncoprotein oligomerization domain. Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Nat. Struct. Biol. 9, 117-20, (2002). PMID: 11780146
2.The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner. Laurent CE, Smithgall TE. Exp. Cell Res. 299, 188-98, (2004). View articlePMID: 15302586
3.BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility. Zheng X, Guller S, Beissert T, Puccetti E, Ruthardt M. BMC Cancer 6, 262, (2006). View articlePMID: 17090304