Reviewed,
UniProtKB/Swiss-Prot P36551 (HEM6_HUMAN)
Last modified
November 3, 2009.
Version 108.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Coproporphyrinogen-III oxidase, mitochondrial Short name=Coproporphyrinogenase Short name=Coprogen oxidase Short name=COX EC=1.3.3.3 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 454 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Catalytic activity | Coproporphyrinogen-III + O2 + 2 H+ = protoporphyrinogen-IX + 2 CO2 + 2 H2O. |
| Pathway | |
| Subcellular location | |
| Involvement in disease | 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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 |
| Sequence similarities | Belongs to the aerobic coproporphyrinogen-III oxidase family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Heme biosynthesis Porphyrin biosynthesis |
| Cellular component | Mitochondrion |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Domain | Transit peptide |
| Molecular function | Oxidoreductase |
| PTM | Acetylation |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | heme biosynthetic process Ref.7 Traceable author statement. Source: ProtInc oxidation reductionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | mitochondrial intermembrane space Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | coproporphyrinogen oxidase activity Ref.16 Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 110 | 110 | Mitochondrion By similarity | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Chain | 111 – 454 | 344 | Coproporphyrinogen-III oxidase, mitochondrial | PRO_0000006029 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 371 | 1 | N6-acetyllysine By similarity | |||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 135 | 1 | V → A in HCP. Ref.18 | VAR_023444 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 162 – 168 | 7 | Missing in HCP. | VAR_002151 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 189 | 1 | G → S in HCP; <5% of activity. Ref.11 | VAR_002152 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 197 | 1 | G → W in HCP. Ref.16 | VAR_002153 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 201 | 1 | E → K in HCP. Ref.15 | VAR_002154 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 208 | 1 | S → F in HCP. Ref.17 | VAR_019067 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 214 | 1 | L → R in HCP. Ref.18 | VAR_023445 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 249 | 1 | P → R in HCP. Ref.18 | VAR_023446 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 249 | 1 | P → S in HCP. Ref.15 | VAR_002155 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 272 | 1 | N → H: dbSNP rs1131857. Ref.11 Ref.7 | VAR_002156 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 279 | 1 | G → R in HCP; a patient carrying also the L-12 mutation in ALAD. Ref.19 | VAR_058005 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 280 | 1 | G → R in HCP. Ref.13 | VAR_002157 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 294 | 1 | V → I: dbSNP rs2228056. Ref.11 Ref.3 Ref.5 | VAR_002158 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 295 | 1 | H → D in HCP. Ref.14 | VAR_002159 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 328 | 1 | R → C in HCP. Ref.17 | VAR_019068 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 331 | 1 | R → W in HCP. Ref.10 Ref.17 | VAR_002160 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 352 | 1 | R → C: dbSNP rs11921054. | VAR_048827 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 390 | 1 | Missing in HCP. | VAR_002161 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 404 | 1 | K → E in HCP; harderoporphyria form. Ref.12 | VAR_002162 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 427 | 1 | W → R in HCP. Ref.16 | VAR_002163 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Natural variant | 447 | 1 | R → C in HCP. Ref.17 | VAR_019069 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 247 | 1 | I → T in CAA82250. Ref.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 122 – 128 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 130 – 132 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 138 – 143 | 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 148 – 170 | 23 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 177 – 183 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Turn | 184 – 186 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 187 – 196 | 10 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 198 – 213 | 16 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 216 – 224 | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 237 – 251 | 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 256 – 267 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 273 – 284 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 290 – 305 | 16 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 311 – 322 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 326 – 328 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 330 – 342 | 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 347 – 359 | 13 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 361 – 372 | 12 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 379 – 399 | 21 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 406 – 408 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 409 – 411 | 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 414 – 420 | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 423 – 426 | 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 438 – 447 | 10 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Coproporphyrinogen oxidase: gene organization and description of a mutation leading to exon 6 skipping." Delfau-Larue M.H., Martasek P., Grandchamp B. Hum. Mol. Genet. 3:1325-1330(1994) [PubMed: 7987309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta. |
| [2] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus. |
| [3] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-294. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-294. Tissue: Brain, Placenta and Uterus. |
| [6] | "Molecular cloning, sequencing and expression of cDNA encoding human coproporphyrinogen oxidase." Taketani S., Kohno H., Furukawa T., Yoshinaga T., Tokunaga R. Biochim. Biophys. Acta 1183:547-549(1994) [PubMed: 8286403] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-454. Tissue: Placenta. |
| [7] | "Molecular cloning, sequencing, and functional expression of a cDNA encoding human coproporphyrinogen oxidase." Martasek P., Camadro J.-M., Delfau-Larue M.H., Dumas J.B., Montagne J.J., de Verneuil H., Labbe P., Grandchamp B. Proc. Natl. Acad. Sci. U.S.A. 91:3024-3028(1994) [PubMed: 8159699] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-454, VARIANT HIS-272. Tissue: Foreskin. |
| [8] | "The long, but not the short, presequence of human coproporphyrinogen oxidase is essential for its import and sorting to mitochondria." Susa S., Daimon M., Ono H., Li S., Yoshida T., Kato T. Tohoku J. Exp. Med. 200:39-45(2003) [PubMed: 12862310] [Abstract] Cited for: PROTEOLYTIC PROCESSING. |
| [9] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [10] | "Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms." Martasek P., Nordmann Y., Grandchamp B. Hum. Mol. Genet. 3:477-480(1994) [PubMed: 8012360] [Abstract] Cited for: VARIANT HCP TRP-331. |
| [11] | "Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria." Fujita H., Kondo M., Taketani S., Nomura N., Furuyama K., Akagi R., Nagai T., Terajima M., Galbraith R.A., Sassa S. Hum. Mol. Genet. 3:1807-1810(1994) [PubMed: 7849704] [Abstract] Cited for: VARIANT HCP SER-189, VARIANTS HIS-272 AND ILE-294. |
| [12] | "A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria." Lamoril J., Martasek P., Deybach J.-C., da Silva V., Grandchamp B., Nordmann Y. Hum. Mol. Genet. 4:275-278(1995) [PubMed: 7757079] [Abstract] Cited for: VARIANT HCP GLU-404. |
| [13] | "A novel missense mutation in exon 4 of the human coproporphyrinogen oxidase gene in two patients with hereditary coproporphyria." Daimon M., Gojyou E., Sugawara M., Yamatani K., Tominaga M., Sasaki H. Hum. Genet. 99:199-201(1997) [PubMed: 9048920] [Abstract] Cited for: VARIANT HCP ARG-280. |
| [14] | "Three novel mutations in the coproporphyrinogen oxidase gene." Lamoril J., Deybach J.-C., Puy H., Grandchamp B., Nordmann Y. Hum. Mutat. 9:78-80(1997) [PubMed: 8990017] [Abstract] Cited for: VARIANTS HCP 162-GLN--ALA-168 DEL AND ASP-295. |
| [15] | "Hereditary coproporphyria: exon screening by heteroduplex analysis detects three novel mutations in the coproporphyrinogen oxidase gene." Schreiber W.E., Zhang X., Senz J., Jamani A. Hum. Mutat. 10:196-200(1997) [PubMed: 9298818] [Abstract] Cited for: VARIANTS HCP LYS-201 AND SER-249. |
| [16] | "Systematic analysis of coproporphyrinogen oxidase gene defects in hereditary coproporphyria and mutation update." Rosipal R., Lamoril J., Puy H., da Silva V., Gouya L., de Rooij F.W.M., Te Velde K., Nordmann Y., Martasek P., Deybach J.-C. Hum. Mutat. 13:44-53(1999) [PubMed: 9888388] [Abstract] Cited for: VARIANTS HCP TRP-197; GLY-390 DEL AND ARG-427. |
| [17] | "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." Wiman A., Floderus Y., Harper P. J. Hum. Genet. 47:407-412(2002) [PubMed: 12181641] [Abstract] Cited for: VARIANTS HCP PHE-208; CYS-328; TRP-331 AND CYS-447. |
| [18] | "Biochemical and genetic characterization of four cases of hereditary coproporphyria in Spain." To-Figueras J., Badenas C., Enriquez M.T., Segura S., Alvarez C., Mila M., Lecha M., Herrero C. Mol. Genet. Metab. 85:160-163(2005) [PubMed: 15896662] [Abstract] Cited for: VARIANTS HCP ALA-135; ARG-214 AND ARG-249. |
| [19] | "Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient." Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S. Br. J. Haematol. 132:237-243(2006) [PubMed: 16398658] [Abstract] Cited for: VARIANT HCP ARG-279. |
| [20] | Erratum Akagi R., Inoue R., Muranaka S., Tahara T., Taketani S., Anderson K.E., Phillips J.D., Sassa S. Br. J. Haematol. 132:662-662(2006) |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Z34531 Z34808 Genomic DNA. Translation: CAA84292.1. AK290140 mRNA. Translation: BAF82829.1. AK223481 mRNA. Translation: BAD97201.1. CH471052 Genomic DNA. Translation: EAW79854.1. BC017210 mRNA. Translation: AAH17210.1. BC023551 mRNA. Translation: AAH23551.1. BC023554 mRNA. Translation: AAH23554.1. D16611 mRNA. Translation: BAA04033.1. Different initiation. Z28409 mRNA. Translation: CAA82250.1. | |||||||||||||
| IPI | IPI00093057. | ||||||||||||
| PIR | I52444. | ||||||||||||
| RefSeq | NP_000088.3. | ||||||||||||
| UniGene | Hs.476982 | ||||||||||||
3D structure databases | |||||||||||||
| |||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| STRING | P36551. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | P36551. | ||||||||||||
Proteomic databases | |||||||||||||
| PeptideAtlas | P36551. | ||||||||||||
| PRIDE | P36551. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000264193; ENSP00000264193; ENSG00000080819; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 1371. | ||||||||||||
| KEGG | hsa:1371. | ||||||||||||
| NMPDR | fig|9606.3.peg.22874. | ||||||||||||
| UCSC | uc003dsx.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 1371. | ||||||||||||
| GeneCards | GC03M099780. | ||||||||||||
| H-InvDB | HIX0003491. | ||||||||||||
| HGNC | HGNC:2321. CPOX. | ||||||||||||
| HPA | HPA015736. | ||||||||||||
| MIM | 121300. phenotype. 612732. gene. | ||||||||||||
| Orphanet | 79273. Coproporphyria, hereditary. | ||||||||||||
| PharmGKB | PA134979958. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | P36551. | ||||||||||||
| HOVERGEN | P36551. | ||||||||||||
| OMA | VFKPWCD. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 1.3.3.3. 247. | ||||||||||||
| Reactome | REACT_9431. Metabolism of porphyrins. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | P36551. | ||||||||||||
| Bgee | P36551. | ||||||||||||
| CleanEx | HS_CPO. HS_CPOX. | ||||||||||||
| Genevestigator | P36551. | ||||||||||||
| GermOnline | ENSG00000080819. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR001260. Coprogen_oxidas. IPR018375. Coproporphyrinogen-3_ox_CS. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:3.40.1500.10. Coprogen_oxidas. 1 hit. | ||||||||||||
| PANTHER | PTHR10755. Coprogen_oxidas. 1 hit. | ||||||||||||
| Pfam | PF01218. Coprogen_oxidas. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00073. COPRGNOXDASE. | ||||||||||||
| PROSITE | PS01021. COPROGEN_OXIDASE. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 5561. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | HEM6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P36551 Secondary accession number(s): A8K275 Q96AF3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


