Uroporphyrinogen-III synthase (UROS)
The protein contains 265 amino acids for an estimated molecular weight of 28628 Da.
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. 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). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
Biological Process
Cellular response to amine stimulus
Cellular response to arsenic-containing substance
Heme biosynthetic process
Porphyrin-containing compound metabolic process
Protoporphyrinogen IX biosynthetic process
Response to antibiotic
Response to platinum ion
Small molecule metabolic process
Uroporphyrinogen III biosynthetic process
Molecular Function
Folic acid binding
Obsolete cofactor binding
Uroporphyrinogen-III synthase activity
The reference OMIM entry for this protein is 263700
Porphyria, congenital erythropoietic
Cep
Gunther disease
Uroporphyrinogen iii synthase deficiency
Uros deficiency
A number sign (#) is used with this entry because congenital erythropoietic porphyria (CEP) is caused by homozygous or compound heterozygous mutation in the uroporphyrinogen III synthase gene (UROS; 606938) on chromosome 10q.
DESCRIPTION
The porphyrias are diseases caused by defects in heme synthesis, 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 (Gross et al., 2000). Desnick and Astrin (2002) provided a comprehensive review of congenital erythropoietic porphyria pathogenesis and treatment. One patient with a phenotype suggestive of congenital erythropoietic anemia was found to have a mutation in the GATA1 gene (305371.0010) that affected UROS expression (see XLTT, 314050).CLINICAL FEATURES
The most dramatic form of genetic porphyria is that which was early recognized as an inborn error of metabolism by Gunther (Dean, 1972). It is associated with lifelong overproduction of series I porphyrins which circulate and are deposited in many tissues, causing light-sensitization and severe damage to skin beginning in childhood. Blistering and scarring of exposed areas may lead to mutilating deformity. Hypertrichosis is sometimes severe. Uroporphyrin I and coproporphyrin I are found in plasma, red blood cells, urine, and feces. Red urine may be observed from infancy, and the teeth become stained red. Hemolytic anemia, an additional complication, may be helped by splenectomy (Meyer and Schmid, 1978). Gunther called this condition congenital haematoporphyria. Watson et al. (1956) renamed it erythropoietic porphyria. Nordmann et al. (1990) described an infant girl who had inherited Gunther disease from both parents and coproporphyria (121300) from her mother. In the newborn period the patient developed intense jaundice with hepatosplenomegaly associated with diffuse bleeding and thrombocytopenia. On the tenth day of life the baby showed a rash with blisters on the backs of the hands and red discoloration of the urine. Porphyria was established by high levels of porphyrins in the urine, feces, and blood. During the next 2 years transfusions were required because of hemolysis. Skin photosensitivity with blistering, fragility, hypertrichosis of the face, and erythrodontia developed. Somatic and mental development were poor. Each of the 2 forms of porphyria was established by enzymatic study. The biologic features of coproporphyria predominated during the first days of life. - Adult-Onset Form Deybach et al. (1981) described a mild form of congenital erythropoietic porphyria with onset in adulthood. Rank et al. (1990) reported what they stated to be the sixth report of adult onset of congenital erythropoietic porphyria. A beneficial effect of hematin therapy was observed. Murphy et al. (1995) described a man who developed cutaneous signs of congenital erythropoietic porphyria at the age of 65 years, 5 years after the onset of symptomatic thrombocytopenia. Persistent thrombocytopenia unresponsive to corticosteroids and immunoglobulin necessitated a splenectomy. Photosensitivity, hemolytic anemia, and hypersplenism are prominent features of adult-onset Gunther disease and thrombocytopenia had been documented in several cases. In the patient reported by Murphy et al. (1995), platelet sequestration studies implicated the spleen as the major site of platele ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 263700 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed