Uroporphyrinogen III synthase

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Uroporphyrinogen-III synthase
Uroporphyrinogen-III synthase
	Uroporphyrinogen-III synthase monomer, Thermus thermophilus
Identifiers
EC no.	4.2.1.75
CAS no.	37340-55-9
Databases
BRENDA	enzyme data
ExPASy	NiceZyme view
KEGG	enzyme entry
MetaCyc	metabolic pathway
Rhea	reactions
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
PMC
Search
PMC	articles
PubMed	articles
NCBI	proteins

UROS
Identifiers
Aliases	UROS, UROIIIS, uroporphyrinogen III synthase
External IDs	OMIM: 606938; MGI: 98917; GeneCards: UROS
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1JR2
Enzyme activity
Gene location (Human)
Chr.	Chromosome 10 (human)
End	125,823,258 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	133,311,801 bp
RNA expression pattern
	Top expressed in
	nucleus accumbens; ; caudate nucleus; ; amygdala; ; right frontal lobe; ; putamen; ; cingulate gyrus; ; anterior cingulate cortex; ; apex of heart; ; prefrontal cortex; ; dorsolateral prefrontal cortex;
	Top expressed in
	fetal liver hematopoietic progenitor cell; ; tibiofemoral joint; ; right kidney; ; right ventricle; ; proximal tubule; ; interventricular septum; ; spleen; ; brown adipose tissue; ; human fetus; ; temporal muscle;
	More reference expression data
	n/a
Gene ontology
Molecular function	lyase activity; uroporphyrinogen-III synthase activity;
Cellular component	cytosol; mitochondrion;
Biological process	tetrapyrrole biosynthetic process; cellular response to amine stimulus; response to antibiotic; heme biosynthetic process; protoporphyrinogen IX biosynthetic process; uroporphyrinogen III biosynthetic process; cellular response to arsenic-containing substance; porphyrin-containing compound biosynthetic process; response to platinum ion;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	7390
	22276
	ENSG00000188690
	ENSMUSG00000030979
	P10746; Q5T3L9
	P51163
	NM_000375; NM_001324036; NM_001324037; NM_001324038; NM_001324039
	NM_001302085; NM_001302086; NM_001302087; NM_009479; NM_001360164
	NP_000366; NP_001310965; NP_001310966; NP_001310967; NP_001310968
	NP_001289014; NP_001289015; NP_001289016; NP_033505; NP_001347093
	Wikidata
View/Edit Human	View/Edit Mouse

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

1jr2 / SCOPe / SUPFAM

Available protein structures:
PDB	IPR003754 PF02602 (ECOD; PDBsum)
AlphaFold	IPR003754 PF02602

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 hydroxymethylbilane 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. The enzyme folds into two alpha/beta domains connected by a beta-ladder, the active site being located between the two domains.

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

Function

The enzyme catalyses the cyclisation reaction of hydroxymethylbilane into uroporphyrinogen III via a spiro intermediate which allows one of the pyrrole rings to convert its initial acetate to propionate configuration into a propionate-acetate one.

hydroxymethylbilane

H₂O

Rightward reaction arrow with minor product(s) to top and bottom right

H₂O

uroporphyrinogen III

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.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000188690 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030979 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Raux E, Schubert HL, Warren MJ (December 2000). "Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum". Cell. Mol. Life Sci. 57 (13–14): 1880–93. doi:10.1007/PL00000670. PMC 11147154. PMID 11215515. S2CID 583311.
↑ Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP (November 2001). "Crystal structure of human uroporphyrinogen III synthase". EMBO J. 20 (21): 5832–9. doi:10.1093/emboj/20.21.5832. PMC 125291. PMID 11689424.
↑ Battersby, Alan R.; Fookes, Christopher J. R.; Matcham, George W.J.; McDonald, Edward (1980). "Biosynthesis of the pigments of life: formation of the macrocycle". Nature. 285 (5759): 17–21. Bibcode:1980Natur.285...17B. doi:10.1038/285017a0. PMID 6769048. S2CID 9070849.
↑ Enzyme 4.2.1.75 at KEGG Pathway Database.
↑ To-Figueras J, Badenas C, Mascaro JM, Madrigal I, Merino A, Bastida P, Lecha M, Herrero C (2007). "Study of the genotype-phenotype relationship in four cases of congenital erythropoietic porphyria". Blood Cells Mol. Dis. 38 (3): 242–6. doi:10.1016/j.bcmd.2006.12.001. PMID 17270473.

External links

Uroporphyrinogen+III+synthase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR003754

This lyase article is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000188690 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030979 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid11215515-5] Raux E, Schubert HL, Warren MJ (December 2000). "Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum". Cell. Mol. Life Sci. 57 (13–14): 1880–93. doi:10.1007/PL00000670. PMC 11147154. PMID 11215515. S2CID 583311.

[pmid11689424-6] Mathews MA, Schubert HL, Whitby FG, Alexander KJ, Schadick K, Bergonia HA, Phillips JD, Hill CP (November 2001). "Crystal structure of human uroporphyrinogen III synthase". EMBO J. 20 (21): 5832–9. doi:10.1093/emboj/20.21.5832. PMC 125291. PMID 11689424.

[7] Battersby, Alan R.; Fookes, Christopher J. R.; Matcham, George W.J.; McDonald, Edward (1980). "Biosynthesis of the pigments of life: formation of the macrocycle". Nature. 285 (5759): 17–21. Bibcode:1980Natur.285...17B. doi:10.1038/285017a0. PMID 6769048. S2CID 9070849.

[8] Enzyme 4.2.1.75 at KEGG Pathway Database.

[pmid17270473-9] To-Figueras J, Badenas C, Mascaro JM, Madrigal I, Merino A, Bastida P, Lecha M, Herrero C (2007). "Study of the genotype-phenotype relationship in four cases of congenital erythropoietic porphyria". Blood Cells Mol. Dis. 38 (3): 242–6. doi:10.1016/j.bcmd.2006.12.001. PMID 17270473.

v t e Carbon–oxygen lyases (EC 4.2) (primarily dehydratases)
4.2.1: Hydro-Lyases	Carbonic anhydrase Fumarase Aconitase Enolase Alpha Enolase 2 Enoyl-CoA hydratase Methylglutaconyl-CoA hydratase Tryptophan synthase Cystathionine beta synthase Porphobilinogen synthase 3-Isopropylmalate dehydratase Urocanase Uroporphyrinogen III synthase Nitrile hydratase
4.2.2: Acting on polysaccharides	Hyaluronate lyase Pectin lyase
4.2.3: Acting on phosphates	Threonine synthase
4.2.99: Other	Carboxymethyloxysuccinate lyase Hydroperoxide lyase Thebaine synthase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)