Uroporphyrinogen decarboxylase (UROD)
The protein contains 367 amino acids for an estimated molecular weight of 40787 Da.
Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III. (updated: March 4, 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.
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The reference OMIM entry for this protein is 176100
Porphyria cutanea tarda
Pct
Porphyria cutanea tarda, type ii
Pct, type ii
Pct, 'familial' type
Porphyria, hepatocutaneous type
Uroporphyrinogen decarboxylase deficiency
Urod deficiency porphyria, hepatoerythropoietic, included; hep, inc
A number sign (#) is used with this entry because porphyria cutanea tarda type II, or familial PCT, is caused by heterozygous mutation in the gene encoding uroporphyrinogen decarboxylase (UROD; 613521). Hepatoerythropoietic porphyria (HEP) is caused by homozygous or compound heterozygous mutation in the UROD gene.
DESCRIPTION
Porphyria cutanea tarda (PCT) is characterized by light-sensitive dermatitis and the excretion of large amounts of uroporphyrin in urine (Elder et al., 1980). De Verneuil et al. (1978) and others classified porphyria cutanea tarda, the most common type of porphyria, into 2 types: type I (176090), or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type, characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). PCT type II is an autosomal dominant disorder with low penetrance and constitutes about 20% of cases of PCT. Recognized exacerbating factors of PCT include iron overload, excessive use of alcohol, exposure to polyhalogenated aromatic chemicals, exposure to estrogens, chronic viral hepatitis C, HIV infections, and mutation in the HFE gene (613609) that are responsible for hereditary hemochromatosis (235200) (review by Lambrecht et al., 2007).CLINICAL FEATURES
Onset of light-sensitive dermatitis in later adult life, associated with the excretion of large amounts of uroporphyrin in urine, characterizes porphyria cutanea tarda, which was so named by Waldenstrom (1937). On areas of skin exposed to sunlight, especially the face, ears, and backs of the hands, chronic ulcerating lesions commence as blisters, and the skin may also be mechanically fragile (Grossman et al., 1979). Hyperpigmentation and hypertrichosis also occur. Acute neuropathic episodes do not occur in this form of porphyria. Onset is often associated with alcoholism, and occasionally with exposure to other agents, such as estrogens. Iron overload is frequently present, and may be associated, coincidentally or causally, with varying degrees of liver damage or fibrosis; liver histology may be characteristic (Cortes et al., 1980). On biopsy, liver parenchyma cells are also loaded with porphyrins and fluoresce bright red in ultraviolet light. The skin lesions are distinctly related to circulating porphyrins (Holti et al., 1958). Malina and Lim (1988) described a 29-year-old woman who first presented with blisters and erosions on the dorsum of the fingers and hands bilaterally 3 weeks after delivery of her second child. The diagnosis of PCT was established enzymatically and by porphyrin studies. Reduced red cell UROD activity was found also in the newborn child and in the patient's mother. Classic congenital erythropoietic porphyria (263700) is due to deficiency of uroporphyrinogen III cosynthase. Kushner et al. (1982) described a remarkable 51-year-old man with congenital erythropoietic porphyria (Gunther disease), first manifested in infancy with eventual development of mutilating skin photosensitivity. The morphologic features of dyserythropoietic bone marrow cells, studied by light and electron microscopy, were identical to those found in congenital dyserythropoietic anemia type I (224120); such had been described before in Gunther disease. A red-orange nuclear fluorescence is not seen in type I dyserythropoietic anemia. The patient of Kushne ... 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 176100 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed