Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial (CPOX)
The protein contains 454 amino acids for an estimated molecular weight of 50152 Da.
Involved in the heme biosynthesis. Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX. (updated: June 7, 2005)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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
Heme biosynthetic process
Protoporphyrinogen IX biosynthetic process
Protoporphyrinogen IX biosynthetic process from glutamate
Response to arsenic-containing substance
Response to insecticide
Response to iron ion
Response to lead ion
Response to methylmercury
Cellular Component
Cytoplasm
Cytosol
Mitochondrial inner membrane
Mitochondrial intermembrane space
Mitochondrion
The reference OMIM entry for this protein is 121300
Coproporphyria, hereditary; hcp
Coproporphyrinogen oxidase deficiency
Cpox deficiency
Cpo deficiency
Cpx deficiency harderoporphyria, included
A number sign (#) is used with this entry because hereditary coproporphyria (HCP) is caused by heterozygous mutation in the CPOX gene (612732) on chromosome 3q12. Harderoporphyria is a distinctive subtype of HCP, caused by homozygous or compound heterozygous mutation in the CPOX gene.
DESCRIPTION
Hereditary coproporphyria, an acute hepatic porphyria, is characterized by acute attacks of neurologic dysfunction often provoked by drugs, fasting, menstrual cycle, or infectious diseases. Skin photosensitivity may also be present. Inheritance is usually autosomal dominant, but autosomal recessive inheritance can also occur. Excretion of large amounts of coproporphyrin III, mostly in feces and urine, is observed. Harderoporphyria is a rare homozygous erythropoietic variant form of HCP, characterized by neonatal hemolytic anemia, sometimes accompanied by skin lesions, and massive excretion of harderoporphyrin in feces. During childhood and adulthood, a mild residual anemia is chronically observed (review by Schmitt et al., 2005).CLINICAL FEATURES
The first case of coproporphyria, reported by Berger and Goldberg (1955), was the offspring of first-cousin parents, both of whom showed excessive excretion of coproporphyrin III. The authors suggested that the disorder is autosomal dominant and that their proband was homozygous. Barnes and Whittaker (1965) described 4 of 5 sibs who were affected. The parents were not tested. Marked elevation of coproporphyria in the feces differentiated the condition from acute intermittent porphyria (AIP; 176000) in which stool porphyrins are usually normal and from variegate porphyria (VP; 176200) in which both coproporphyrin and protoporphyrin fractions are increased in the stool. The proband experienced typical acute porphyria. Constipation and abdominal colic were striking features in these patients. Goldberg et al. (1967) added 20 new cases. A massive excretion of coproporphyrin III in the urine and predominantly in the feces was demonstrated. Attacks resembling those of AIP were precipitated by drugs, and during attacks porphobilinogen and delta-aminolevulinic acid were excreted in the urine in excess. Photosensitivity is occasionally present and the only manifestations may be psychiatric. About half of cases are asymptomatic. This is an hepatic form of porphyria. In the family of Haeger-Aronsen et al. (1968), 13 persons in 5 sibships of 2 generations showed latent coproporphyria, in addition to the symptomatic proband. Cripps and Peters (1970) found that tranquilizers, including meprobamate and chlorpromazine, precipitated attacks. McIntyre et al. (1971) noted that increased hepatic delta-aminolevulinic acid synthetase has been demonstrated in 3 forms of hereditary porphyria: AIP, VP, and coproporphyria. In cultured skin fibroblasts, Elder et al. (1976) found that the activity of coproporphyrinogen oxidase was about half normal. Similar findings were reported for leukocytes (Brodie et al., 1977). In the homozygous patient reported by Grandchamp et al. (1977), activity of coproporphyrinogen oxidase was only 2% of control values. Andrews et al. (1984) found 27 cases of coproporphyria in a kindred in which 135 members were screened for fecal porphyrins. Of the 135, 6 females and 1 male had probably suffered clinical attacks; the M:F ratio of cases revealed by screening was 13:14. The proband had her first attack at age 84 years; diazepam and nitrazepam were incriminated in her attack, and o ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 121300 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).