Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. H2O + 4 porphobilinogen = hydroxymethylbilane + 4 NH4(+) Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4. Belongs to the HMBS family. This sequence may not function as a hydroxymethylbilane synthase because it lacks the cysteine residue necessary for attachment of the dipyrromethane cofactor.