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. 2021 Sep 15;13(9):1478. doi: 10.3390/pharmaceutics13091478

Figure 2.

Figure 2

Schematic representation of the wild-type and the rearranged BRAF gene. All BRAF rearrangements lead to a break leaving the serine/threonine kinase domain (or conserved region 3) and the ATP binding pocket of BRAF intact, while the N-terminal domains (conserved region 1 (CR1) and conserved region 2 (CR2)) are lost, replaced by the fusion partner. Since CR1 is known to auto-inhibit the kinase domain of the BRAF protein, its loss constitutively activates the kinase and explains the oncogenic potential of the rearrangement. KIAA1549 is the most frequent BRAF fusion partner (associated with pilocytic astrocytoma), but 40 other partners have also been described (https://ccsm.uth.edu/FusionGDB/, (accessed on 20 August 2021)), such as AGK and MKRN1 (reported as acquired resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR-mutant lung adenocarcinoma). Abbreviations: AGK, AcylGlycerol kinase; BRS, BRAF-specific region; CR1-3, conserved region 1-3; CRD, Cys-rich domain; KD, kinase domain; MKRN1, Makorin ring finger protein 1; RBD, Raf-like Ras-binding domain.