Skip to main content
. 2017 Nov 30;9(12):164. doi: 10.3390/cancers9120164

Figure 3.

Figure 3

Schematic structural composition of ALK fusion proteins. (A) EML4-ALK fusion proteins. The breakpoint in the ALK gene is at exon 20; the breakpoint in EML4 is at different exons (e.g., 2, 6, 13, 14, 15, 18, and 20), resulting in variable EML4-ALK fusion proteins. In detail, variant 1 (E13;A20) and variant 2 (E20;A20) contain exons 1 to 13 and 1 to 20 of EML4, respectively, fused to exon 20 of ALK. Thus, the portion of EML4 includes its C-terminal coiled coil domain, HELP domain and parts of the WD repeat domain of EML4. Variant 3a/b EML4-ALK fusion proteins (E6a/b;A20) consist of exons 1 to 6 of EML4, with exon 6b being 188bp downstream of exon 6a, fused to exon 20 of ALK. Variant 4 (E14;E20) contain exons 1 to 14 of EML4, insertion of four amino acids of unknown origin, and fusion to exon 20 of ALK N-terminally lacking 49bp. Variant 5 EML4-ALK fusion proteins (E2a/b;A20) present a fusion of exon 2 of EML4 to exon 20 of ALK (E2a;A20) or to 117bp upstream of exon 20 of ALK (E2b;A20). Variant 6 (E13b;A20) contains exons 1 to 13 of EML4 fused to exon 20 of ALK with an insertion of 19 amino acids derived from upstream intron 19. Variant 7 (E14;A20) represents a genetic fusion of EML4 at exon 14 with ALK at exon 20, the latter lacking the first four amino acids. Variant “4” (E15;A20) is characterized as a fusion product of EML4 at exon 15 and ALK at exon 20. Variant “5” (E18;E20) consists of exons 1 to 18 of EML4 fused to exon 20 of ALK. (B) Other X-ALK fusion proteins. X represents any fusion partner including, amongst others, KIF5B-ALK (K24;A20 and K15;A20), TFG-ALK (T3;A20), DCTN1-ALK (D26;A20), SQSTM1-ALK (S5;A20), TPR-ALK (T15;A20), STRN-ALK (S3;A20), HIP1-ALK (H21;A20), and CLTC-ALK (C31;A20). For (A) and (B), protein domains are indicated by color and include: coiled coil (CC, light orange), HELP (dark orange), WD repeats (dark green), ALK kinase domain (blue), kinesin (ocher), PB1 (dark grey), CAP-Gly (light green), dynactin (dark red), zinc finger (ZZ, light violet), striatin (dark violet), ANTH (light yellow), clathrin-binding (light red), clathrin propeller (olive green), clathrin link (light grey), and clathrin (petrol) domains. Protein domains are derived from Pfam database [52]. See Table 1 for a list of ALK fusion partners and encoded protein domains.