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UROS

Function

Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins (PubMed:11689424, PubMed:18004775). Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme).

Involvement in disease

Congenital erythropoietic porphyria

CEP

Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. The manifestations of CEP are heterogeneous, ranging from nonimmune hydrops fetalis due to severe hemolytic anemia in utero to milder, later onset forms, which have only skin lesions due to cutaneous photosensitivity in adult life. The deficiency in UROS activity results in the non-enzymatic conversion of hydroxymethylbilane (HMB) into the uroporphyrinogen-I isomer.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Porphyrin-containing compound metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 3/4.

Sequence Similarities

Belongs to the uroporphyrinogen-III synthase family.

Tissue Specificity

Ubiquitous.

Alternative names

Uroporphyrinogen-III synthase, UROIIIS, UROS, Hydroxymethylbilane hydrolyase [cyclizing], Uroporphyrinogen-III cosynthase

swissprot:P10746 omim:606938 entrezGene:7390