protein activator of interferon induced protein kinase EIF2AK2
The PRKRA gene provides instructions for making a protein called PACT. This protein plays a role in the cell's response to stress, such as exposure to viruses, damaging molecules called free radicals, or other toxic substances. When a cell is under stress, the PACT protein turns on (activates) another protein called PKR, which then turns off (inactivates) the eIF2 alpha (eIF2α) protein. Inactivation of eIF2α lowers protein production, which helps protect cells from damage. The signals triggered by PACT can ultimately lead to self-destruction (apoptosis) of the cell if it remains under stress.
The signals sent by the PACT protein are also important for a process in the brain called synaptic plasticity. Synaptic plasticity is the ability of the connections between brain cells (synapses) to change and adapt over time in response to experience. This process is critical for learning and memory.
At least eight mutations in the PRKRA gene have been identified in people with dystonia 16. This condition is one of many forms of dystonia, which is a group of conditions characterized by involuntary movements, twisting (torsion) and tensing of various muscles, and unusual positioning of affected body parts.
Most of the PRKRA gene mutations that cause dystonia 16 change single protein building blocks (amino acids) in the PACT protein. Studies suggest that these changes alter the timing of signals sent by the PACT protein in response to stress. The abnormal signaling increases the rate at which cell death occurs. It is likely that the excessive loss of cells in certain regions of the brain impairs the brain's ability to control muscles and movement, resulting in the features of dystonia 16. It is unclear why brain cells are particularly affected by PRKRA gene mutations.
- PRKRA gene
- protein activator of the interferon-induced protein kinase