CPOX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2AEX
Identifiers
Aliases	CPOX, CPO, CPX, HCP, coproporphyrinogen oxidase, COX, HARPO
External IDs	OMIM: 612732; MGI: 104841; HomoloGene: 76; GeneCards: CPOX; OMA:CPOX - orthologs
EC number	1.3.3.3
Gene location (Mouse) Chr. Chromosome 16 (mouse)[1] Band 16|16 C1.2 Start 58,490,655 bp[1] End 58,537,999 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in trabecular bone jejunal mucosa corpus callosum right lobe of liver bone marrow inferior ganglion of vagus nerve bone marrow cells rectum monocyte duodenum Top expressed in human fetus atrium tibiofemoral joint fetal liver hematopoietic progenitor cell yolk sac epithelium of small intestine right kidney pontine nuclei ventral tegmental area habenula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function coproporphyrinogen oxidase activity protein homodimerization activity structural constituent of eye lens identical protein binding oxidoreductase activity Cellular component membrane mitochondrial intermembrane space mitochondrion mitochondrial inner membrane cytosol cytoplasm Biological process response to arsenic-containing substance protoporphyrinogen IX biosynthetic process porphyrin-containing compound biosynthetic process response to iron ion heme biosynthetic process response to lead ion response to inorganic substance response to insecticide response to methylmercury protoporphyrinogen IX biosynthetic process from glutamate Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1371 12892 Ensembl n/a ENSMUSG00000022742 UniProt P36551 P36552 RefSeq (mRNA) NM_000097 NM_007757 RefSeq (protein) NP_000088 NP_031783 Location (UCSC) n/a Chr 16: 58.49 – 58.54 Mb PubMed search [2] [3]
Wikidata
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Coprogen oxidase
coproporphyrinogen iii oxidase from leishmania major
Identifiers
Symbol	Coprogen oxidase
Pfam	PF01218
InterPro	IPR001260
PROSITE	PDOC00783
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Coproporphyrinogen-III oxidase, mitochondrial (abbreviated as CPOX) is an enzyme that in humans is encoded by the CPOX gene.^[4][5][6] A genetic defect in the enzyme results in a reduced production of heme in animals. The medical condition associated with this enzyme defect is called hereditary coproporphyria.^[7][8]

CPOX, the sixth enzyme of the haem biosynthetic pathway, converts coproporphyrinogen III to protoporphyrinogen IX through two sequential steps of oxidative decarboxylation.^[9] The activity of the CPOX enzyme, located in the mitochondrial membrane, is measured in lymphocytes.^[10]

CPOX is an enzyme involved in the sixth step of porphyrin metabolism it catalyses the oxidative decarboxylation of coproporphyrinogen III to proto-porphyrinogen IX in the haem and chlorophyll biosynthetic pathways.^[5][11] The protein is a homodimer containing two internally bound iron atoms per molecule of native protein.^[12] The enzyme is active in the presence of molecular oxygen that acts as an electron acceptor. The enzyme is widely distributed having been found in a variety of eukaryotic and prokaryotic sources.

Human CPOX is a mitochondrial enzyme encoded by a 14 kb CPOX gene containing seven exons located on chromosome 3 at q11.2.^[6]

CPOX is expressed as a 40 kDa precursor and contains an amino terminal mitochondrial targeting signal.^[13] After proteolytic processing, the protein is present as a mature form of a homodimer with a molecular mass of 37 kDa.^[14]

Hereditary coproporphyria (HCP) and harderoporphyria are two phenotypically separate disorders that concern partial deficiency of CPOX. Neurovisceral symptomatology predominates in HCP. Additionally, it may be associated with abdominal pain and/or skin photosensitivity. Hyper-excretion of coproporphyrin III in urine and faeces has been recorded in biochemical tests.^[15] HCP is an autosomal dominant inherited disorder, whereas harderoporphyria is a rare erythropoietic variant form of HCP and is inherited in an autosomal recessive fashion. Clinically, it is characterized by neonatal haemolytic anaemia. Sometimes, the presence of skin lesions with marked faecal excretion of harderoporphyrin is also described in harderoporphyric patients.^[16]

To date, over 50 CPOX mutations causing HCP have been described.^[17] Most of these mutations result in substitution of amino acid residues within the structural framework of CPOX.^[18] At least 32 of these mutations are considered to be disease-causing mutations.^[19] In terms of the molecular basis of HCP and harderoporphyria, mutations of CPOX in patients with harderoporphyria were demonstrated in the region of exon 6, where mutations in those with HCP were also identified.^[20] As only patients with mutation in this region (K404E) would develop harderoporphyria, this mutation led to diminishment of the second step of the decarboxylation reaction during the conversion of coproporphyrinogen to protoporphyrinogen, implying that the active site of the enzyme involved in the second step of decarboxylation is located in exon 6.^[17]

CPOX has been shown to interact with the atypical keto-isocoproporphyrin (KICP) in human subjects with mercury (Hg) exposure.^[21]

• Coproporphyrinogen+III+Oxidases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)