Uroporphyrinogen III synthase

Uroporphyrinogen III synthase (EC 4.2.1.75) is an enzyme involved in the metabolism of the cyclic tetrapyrrole compound porphyrin. It is involved in the conversion of hydroxymethyl bilane into uroporphyrinogen III. This enzyme catalyses the inversion of the final pyrrole unit (ring D) of the linear tetrapyrrole molecule, linking it to the first pyrrole unit (ring A), thereby generating a large macrocyclic structure, uroporphyrinogen III.^[1] The enzyme folds into two alpha/beta domains connected by a beta-ladder, the active site being located between the two domains.^[2]

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Uroporphyrinogen-III synthase
Uroporphyrinogen-III synthase monomer, Thermus thermophilus
Identifiers
EC no.	4.2.1.75
CAS no.	37340-55-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
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Uroporphyrinogen III synthase
Identifiers
Symbol	UROS
NCBI gene	7390
HGNC	12592
OMIM	606938
RefSeq	NM_000375
UniProt	P10746
Other data
EC number	4.2.1.75
Locus	Chr. 10 q25.2-26.3
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Uroporphyrinogen-III synthase HemD
crystal structure of uroporphyrinogen iii synthase from an extremely thermophilic bacterium thermus thermophilus hb8 (wild type, native, form-2 crystal)
Identifiers
Symbol	HEM4
Pfam	PF02602
InterPro	IPR003754
SCOP2	1jr2 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Pathology

A deficiency is associated with Gunther's disease, also known as congenital erythropoietic porphyria (CEP). This is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase.^[3]