Figure 3

KIAA1549-BRAF fusion protein. Of the two components of the KIAA1549-BRAF fusion protein, BRAF is a cytosolic serine/threonine kinase that is activated by binding of RAS-GTP. The function of KIAA1549 remains unknown. This fusion merges intron 15 of KIAA1549 and intron 8 of BRAF, although several other configurations of these fused genes have been observed. The kinase domain and ATP binding pocket of BRAF are retained but the N-terminal conserved region 1 (CR1) and conserved region 2 (CR2) are lost. CR1 auto-inhibits the kinase domain, but this inhibitory allosteric interaction is disrupted by the binding of RAS-GTP to CR1. Thus, loss of the CR1 domain suggests a dysregulation of the kinase activity of this fusion.