UROD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JPH, 1JPI, 1JPK, 1R3Q, 1R3R, 1R3S, 1R3T, 1R3V, 1R3W, 1R3Y, 1URO, 2Q6Z, 2Q71, 3GVQ, 3GVR, 3GVV, 3GVW, 3GW0, 3GW3
Identifiers
Aliases	UROD, PCT, UPD, uroporphyrinogen decarboxylase
External IDs	OMIM: 613521 MGI: 98916 HomoloGene: 320 GeneCards: UROD
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.1 Start 45,010,950 bp[1] End 45,015,575 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 D1|4 53.41 cM Start 116,847,162 bp[2] End 116,851,610 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone parotid gland right adrenal gland parietal pleura endothelial cell middle temporal gyrus Brodmann area 23 bone marrow pancreatic ductal cell germinal epithelium Top expressed in internal carotid artery endocardial cushion external carotid artery facial motor nucleus atrioventricular valve medullary collecting duct renal corpuscle lacrimal gland medial ganglionic eminence blood More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding lyase activity uroporphyrinogen decarboxylase activity carboxy-lyase activity Cellular component nucleoplasm cytoplasm cytosol Biological process protoporphyrinogen IX biosynthetic process porphyrin-containing compound biosynthetic process heme biosynthetic process heme metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7389 22275 Ensembl ENSG00000126088 ENSMUSG00000028684 UniProt P06132 P70697 RefSeq (mRNA) NM_000374 NM_009478 RefSeq (protein) NP_000365 NP_033504 Location (UCSC) Chr 1: 45.01 – 45.02 Mb Chr 4: 116.85 – 116.85 Mb PubMed search [3] [4]
Wikidata
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Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme (EC 4.1.1.37) that in humans is encoded by the UROD gene.^[5]

Function

Uroporphyrinogen III decarboxylase is a homodimeric enzyme (PDB: 1URO​) that catalyzes the fifth step in heme biosynthesis, which corresponds to the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III:

uroporphyrinogen III ${\displaystyle \rightleftharpoons }$ coproporphyrinogen III + 4 CO₂

Clinical significance

Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.^[5] At least 65 disease-causing mutations in this gene have been discovered.^[6]

Mechanism

At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO₂ from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions.

UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an arginine residue.^[7] A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 10⁻¹⁹ s⁻¹, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, i.e. catalytic proficiency, is the largest for any enzyme known, 6 x 10²⁴ M⁻¹.^[8]