2aex

Structural highlights

Disease

HEM6_HUMAN Defects in CPOX are the cause of hereditary coproporphyria (HCP) [MIM:121300. HCP is an acute hepatic porphyria and an autosomal dominant disease characterized by neuropsychiatric disturbances and skin photosensitivity. Biochemically, there is an overexcretion of coproporphyrin III in the urine and in the feces. HCP is clinically characterized by attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. The symptoms are generally manifested with rapid onset, and can be precipitated by drugs, alcohol, caloric deprivation, infection, endocrine factors or stress. A severe variant form is harderoporphyria, which is characterized by earlier onset attacks, massive excretion of harderoporphyrin in the feces, and a marked decrease of coproporphyrinogen IX oxidase activity.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Function

HEM6_HUMAN Key enzyme in heme biosynthesis. Catalyzes the oxidative decarboxylation of propionic acid side chains of rings A and B of coproporphyrinogen III.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Martasek P, Nordmann Y, Grandchamp B. Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms. Hum Mol Genet. 1994 Mar;3(3):477-80. PMID:8012360
2. ↑ Fujita H, Kondo M, Taketani S, Nomura N, Furuyama K, Akagi R, Nagai T, Terajima M, Galbraith RA, Sassa S. Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria. Hum Mol Genet. 1994 Oct;3(10):1807-10. PMID:7849704
3. ↑ Lamoril J, Martasek P, Deybach JC, Da Silva V, Grandchamp B, Nordmann Y. A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria. Hum Mol Genet. 1995 Feb;4(2):275-8. PMID:7757079
4. ↑ Daimon M, Gojyou E, Sugawara M, Yamatani K, Tominaga M, Sasaki H. A novel missense mutation in exon 4 of the human coproporphyrinogen oxidase gene in two patients with hereditary coproporphyria. Hum Genet. 1997 Feb;99(2):199-201. PMID:9048920
5. ↑ Lamoril J, Deybach JC, Puy H, Grandchamp B, Nordmann Y. Three novel mutations in the coproporphyrinogen oxidase gene. Hum Mutat. 1997;9(1):78-80. PMID:8990017 doi:<78::AID-HUMU17>3.0.CO;2-M 10.1002/(SICI)1098-1004(1997)9:1<78::AID-HUMU17>3.0.CO;2-M
6. ↑ Schreiber WE, Zhang X, Senz J, Jamani A. Hereditary coproporphyria: exon screening by heteroduplex analysis detects three novel mutations in the coproporphyrinogen oxidase gene. Hum Mutat. 1997;10(3):196-200. PMID:9298818 doi:<196::AID-HUMU3>3.0.CO;2-H 10.1002/(SICI)1098-1004(1997)10:3<196::AID-HUMU3>3.0.CO;2-H
7. ↑ Rosipal R, Lamoril J, Puy H, Da Silva V, Gouya L, De Rooij FW, Te Velde K, Nordmann Y, Martasek P, Deybach JC. Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update. Hum Mutat. 1999;13(1):44-53. PMID:9888388 doi:<44::AID-HUMU5>3.0.CO;2-Q 10.1002/(SICI)1098-1004(1999)13:1<44::AID-HUMU5>3.0.CO;2-Q
8. ↑ Wiman A, Floderus Y, Harper P. Two novel mutations and coexistence of the 991C>T and the 1339C>T mutation on a single allele in the coproporphyrinogen oxidase gene in Swedish patients with hereditary coproporphyria. J Hum Genet. 2002;47(8):407-12. PMID:12181641 doi:10.1007/s100380200059
9. ↑ To-Figueras J, Badenas C, Enriquez MT, Segura S, Alvarez C, Mila M, Lecha M, Herrero C. Biochemical and genetic characterization of four cases of hereditary coproporphyria in Spain. Mol Genet Metab. 2005 Jun;85(2):160-3. Epub 2005 Feb 25. PMID:15896662 doi:10.1016/j.ymgme.2004.12.012
10. ↑ Akagi R, Inoue R, Muranaka S, Tahara T, Taketani S, Anderson KE, Phillips JD, Sassa S. Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient. Br J Haematol. 2006 Jan;132(2):237-43. PMID:16398658 doi:10.1111/j.1365-2141.2005.05852.x