Cloned (Comment) | Organism |
---|---|
expression of wild-type UROIIIS and 25 point mutants in Escherichia coli | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
A104V | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
A66V | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
A69T | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
C73R | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria, the mutant protein retains partial catalytic activity but shows reduced the enzyme stability | Homo sapiens |
E81D | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
G188R | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
G188W | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
G225S | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
G236V | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
H173Y | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
I129T | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
I219S | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
L237P | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
L4F | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
additional information | genotype/phenotype analysis of the studied cases of congenital erythropoietic porphyria, overview | Homo sapiens |
P248Q | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
P53L | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
Q187P | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
S212P | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
S47P | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
T228M | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
T62A | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
V3F | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
V82F | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
V99A | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
Y19C | a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetic and thermodynamic analysis, thermodynamic versus kinetic stability, overview | Homo sapiens | |
0.00015 | - |
Hydroxymethylbilane | pH not specified in the publication, temperature not specified in the publication | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
28000 | - |
x * 28000 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hydroxymethylbilane | Homo sapiens | - |
uroporphyrinogen III + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Pseudomonas syringae | Q88B90 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
additional information | UROIIIS is processed via the proteosome pathway, which can be reverted by reversibly inhibiting the proteosome with the aldehyde MG132 | Homo sapiens |
Purification (Comment) | Organism |
---|---|
recombinant wild-type UROIIIS and 25 point mutants in Escherichia coli to over 97% purity | Homo sapiens |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
hydroxymethylbilane = uroporphyrinogen III + H2O | reaction mechanism, modeling involving Tyr168, overview | Homo sapiens |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
33.37 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hydroxymethylbilane | - |
Homo sapiens | uroporphyrinogen III + H2O | - |
? | |
hydroxymethylbilane | enzymatic conversion of preuroporphyrinogen. The substrate must bind the enzyme in a conformation that prevents C19 from reacting with C20 | Homo sapiens | uroporphyrinogen III + H2O | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 28000 | Homo sapiens |
More | three-dimensional structure, overview | Homo sapiens |
More | three-dimensional structure, overview | Pseudomonas syringae |
Synonyms | Comment | Organism |
---|---|---|
UROIIIS | - |
Homo sapiens |
UROIIIS | - |
Pseudomonas syringae |
Uroporphyrinogen III synthase | - |
Homo sapiens |
Uroporphyrinogen III synthase | - |
Pseudomonas syringae |
Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
---|---|---|---|
additional information | - |
the enzyme is metathermostabile, irreversible denaturation process. At physiological temperature and in vitro, UROIIIS has a half-life time of 61.1 h, a long time for the enzyme to exert its function in the cell, dynamic behavior of the protein, three-state model, overview. Thermodynamic versus kinetic stability, overview | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | congenital erythropoietic porphyria is a rare autosomal disease ultimately related to deleterious mutations in uroporphyrinogen III synthase. In absence or dysfunction of the enzyme, hydroxymethylbilane spontaneously degrades to the by-product uroporphyrinogen I, which cannot lead to the heme group and accumulates in the body, producing some of the symptoms observed in congenital erythropoietic porphyria patients, phenotype, structural and molecular basis, overview | Homo sapiens |
physiological function | UROIIIS is the fourth enzyme of the biosynthetic route of the heme group and catalyzes the cyclization of the linear tetrapyrrol hydroxymethylbilane, inverting the configuration in one of the aromatic rings. It accelerates the production of uroporphyrinogen III (an energetically unfavorable chemical reaction) at the same time as it suppresses the spontaneous reaction pathway to yield uroporphyrinogen I | Homo sapiens |