Genes annotated by the GO term GO:0048037. Interacting selectively with a cofactor, a substance that is required for the activity of an enzyme or other protein. Cofactors may be inorganic, such as the metal atoms zinc, iron, and copper in certain forms, or organic, in which case they are referred to as coenzymes. Cofactors may either be bound tightly to active sites or bind loosely with the substrate.