Table 1.
Effect of UBIAD1 mutations on VKD carboxylation and MK-4 biosynthesis
| Vitamin K-dependent carboxylation | MK-4 synthesis, % | SCD-associate mutation [24] | ||
|---|---|---|---|---|
| Activity ± SD, % | EC50 ± SD, nM | |||
| WT | 100 ± 2.4 | 3.7 ± 0.4 | 100 | - |
| R54A | 79.8 ± 2.6 | 84 ± 11.6 | 47.3 ± 5 | - |
| L67Q | 40.7 ± 2 | 3.8 ± 0.8 | 27.9 ± 2.3 | - |
| N102S | 98.2 ± 3 | 3.9 ± 0.3 | 82.2 ± 17 | Yes |
| D112G | 104.8 ± 3 | 5.1 ± 0.8 | 92.5 ± 3.3 | Yes |
| D112N | 109.6 ± 5.2 | 6.4 ± 0.6 | 110.3 ± 10.8 | Yes |
| C147S | 100.5 ± 3.7 | 3.7 ± 0.6 | 106.1 ± 11.2 | - |
| G177E | 117.1 ± 4.5 | 3.7 ± 0.5 | 123.3 ± 10.9 | Yes |
| G177R | 119.8 ± 1.2 | 3.0 ± 0.3 | 125.9 ± 12.9 | Yes |
| K181A | 101.7 ± 3 | 11.9 ± 0.4 | 62.3 ± 4.8 | - |
| G186R | 57.1 ± 1.1 | 221.1 ± 15.4 | 8.2 ± 6.1 | Yes |
| D236A | 32.5 ± 0.9 | 90 ± 17.6 | 3.3 ± 1.9 | - |
| D236E | 107.1 ± 4.9 | 22.6 ± 2.2 | 26.6 ± 5.4 | Yes |
| D240A | 85.6 ± 1.4 | 64 ± 10.5 | 2.6 ± 2.3 | - |
| D240N | 107.8 ± 2.5 | 11.2 ± 1.5 | 26.9 ± 8.1 | Yes |
Note: The activity of vitamin K-dependent carboxylation was obtained at 1 μM vitamin K3. The EC50 value was obtained using vitamin K3 concentrations from 0.015nM to 1000 nM. MK-4 synthetic activity was determined using 1 μM COT-vitamin K.