UBA1

The UBA1 gene (also called UBE1) provides instructions for making the ubiquitin-activating enzyme E1. This enzyme is involved in a process that targets proteins to be broken down (degraded) within cells. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells.

Ubiquitin-activating enzyme E1 is part of the ubiquitin-proteasome system, which is the cell machinery that breaks down unneeded proteins. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. Ubiquitin-activating enzyme E1 is responsible for the first step in the ubiquitin-proteasome system; it turns on (activates) a small protein called ubiquitin. With the assistance of other proteins, the active ubiquitin attaches to a targeted protein. When a chain of ubiquitin proteins is attached to the targeted protein, the protein is recognized and destroyed by a complex of enzymes called a proteasome.

spinal muscular atrophy - caused by mutations in the UBA1 gene

At least three mutations in the UBA1 gene have been found to cause X-linked infantile spinal muscular atrophy. Each of these mutations changes one DNA building block (nucleotide) in the UBA1 gene. Two of the mutations (written as 1617G>T and 1639A>G) are thought to lead to an enzyme with impaired function. A third mutation (written as 1731C>T) results in a decrease in the activity of the UBA1 gene, causing less of the enzyme to be produced. Reduced levels of functional enzyme can disrupt the process of protein degradation. A buildup of proteins in cells can cause the cell to die; the motor nerve cells that control muscle movement are particularly susceptible to damage from protein buildup.