Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the fourth step in the heme biosynthetic pathway. hydroxymethylbilane = H2O + uroporphyrinogen III Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4. Present with 1360 molecules/cell in log phase SD medium. Belongs to the uroporphyrinogen-III synthase family. Was originally thought to be involved in mitochondrial import.