Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
26  structures 4258  species 0  interactions 5226  sequences 33  architectures

Family: Coprogen_oxidas (PF01218)

Summary: Coproporphyrinogen III oxidase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Coproporphyrinogen III oxidase". More...

Coproporphyrinogen III oxidase Edit Wikipedia article

Available structures
PDBOrtholog search: PDBe RCSB
AliasesCPOX, CPO, CPX, HCP, coproporphyrinogen oxidase, COX
External IDsOMIM: 612732 MGI: 104841 HomoloGene: 76 GeneCards: CPOX
EC number1.3.3.3
Gene location (Human)
Chromosome 3 (human)
Chr.Chromosome 3 (human)[1]
Chromosome 3 (human)
Genomic location for CPOX
Genomic location for CPOX
Band3q11.2Start98,579,446 bp[1]
End98,593,648 bp[1]
RNA expression pattern
PBB GE CPOX 204172 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 3: 98.58 – 98.59 MbChr 16: 58.67 – 58.72 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse
PDB 1vju EBI.jpg
coproporphyrinogen iii oxidase from leishmania major

Coproporphyrinogen-III oxidase, mitochondrial (abbreviated as CPOX) is an enzyme that in humans is encoded by the CPOX gene.[5][6][7] 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.[8][9]

CPOX, the sixth enzyme of the haem biosynthetic pathway, converts coproporphyrinogen III to protoporphyrinogen IX through two sequential steps of oxidative decarboxylation.[10] The activity of the CPOX enzyme, located in the mitochondrial membrane, is measured in lymphocytes.[11]


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.[6][12] The protein is a homodimer containing two internally bound iron atoms per molecule of native protein.[13] 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.[7]


CPOX is expressed as a 40 kDa precursor and contains an amino terminal mitochondrial targeting signal.[14] After proteolytic processing, the protein is present as a mature form of a homodimer with a molecular mass of 37 kDa.[15]

Clinical significance

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.[16] 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.[17]

To date, over 50 CPOX mutations causing HCP have been described.[18] Most of these mutations result in substitution of amino acid residues within the structural framework of CPOX.[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.[18]


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


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000080819 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022742 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Lamoril J, Martasek P, Deybach JC, Da Silva V, Grandchamp B, Nordmann Y (February 1995). "A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria". Human Molecular Genetics. 4 (2): 275–8. doi:10.1093/hmg/4.2.275. PMID 7757079.
  6. ^ a b Kohno H, Furukawa T, Yoshinaga T, Tokunaga R, Taketani S (October 1993). "Coproporphyrinogen oxidase. Purification, molecular cloning, and induction of mRNA during erythroid differentiation". The Journal of Biological Chemistry. 268 (28): 21359–63. PMID 8407975.
  7. ^ a b "Entrez Gene: CPOX coproporphyrinogen oxidase".
  8. ^ "Hereditary coproporphyria". Genetic and Rare Diseases Information Center. National Institutes of Health. Retrieved 8 August 2011.
  9. ^ "CPOX". Genetics Home Reference. Retrieved 8 August 2011.
  10. ^ Sano S, Granick S (April 1961). "Mitochondrial coproporphyrinogen oxidase and protoporphyrin formation". The Journal of Biological Chemistry. 236: 1173–80. PMID 13746277.
  11. ^ Guo R, Lim CK, Peters TJ (October 1988). "Accurate and specific HPLC assay of coproporphyrinogen III oxidase activity in human peripheral leucocytes". Clinica Chimica Acta; International Journal of Clinical Chemistry. 177 (3): 245–52. doi:10.1016/0009-8981(88)90069-1. PMID 3233772.
  12. ^ Madsen O, Sandal L, Sandal NN, Marcker KA (October 1993). "A soybean coproporphyrinogen oxidase gene is highly expressed in root nodules". Plant Molecular Biology. 23 (1): 35–43. doi:10.1007/BF00021417. PMID 8219054.
  13. ^ Camadro JM, Chambon H, Jolles J, Labbe P (May 1986). "Purification and properties of coproporphyrinogen oxidase from the yeast Saccharomyces cerevisiae". European Journal of Biochemistry / FEBS. 156 (3): 579–87. doi:10.1111/j.1432-1033.1986.tb09617.x. PMID 3516695.
  14. ^ Martasek P, Camadro JM, Delfau-Larue MH, Dumas JB, Montagne JJ, de Verneuil H, Labbe P, Grandchamp B (April 1994). "Molecular cloning, sequencing, and functional expression of a cDNA encoding human coproporphyrinogen oxidase". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3024–8. doi:10.1073/pnas.91.8.3024. PMC 43507. PMID 8159699.
  15. ^ Martasek P, Nordmann Y, Grandchamp B (March 1994). "Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms". Human Molecular Genetics. 3 (3): 477–80. doi:10.1093/hmg/3.3.477. PMID 8012360.
  16. ^ Taketani S, Kohno H, Furukawa T, Yoshinaga T, Tokunaga R (January 1994). "Molecular cloning, sequencing and expression of cDNA encoding human coproporphyrinogen oxidase". Biochimica et Biophysica Acta. 1183 (3): 547–9. doi:10.1016/0005-2728(94)90083-3. PMID 8286403.
  17. ^ Kim DH, Hino R, Adachi Y, Kobori A, Taketani S (December 2013). "The enzyme engineering of mutant homodimer and heterodimer of coproporphyinogen oxidase contributes to new insight into hereditary coproporphyria and harderoporphyria". Journal of Biochemistry. 154 (6): 551–9. doi:10.1093/jb/mvt086. PMID 24078084.
  18. ^ a b Hasanoglu A, Balwani M, Kasapkara CS, Ezgü FS, Okur I, Tümer L, Cakmak A, Nazarenko I, Yu C, Clavero S, Bishop DF, Desnick RJ (February 2011). "Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R". Journal of Inherited Metabolic Disease. 34 (1): 225–31. doi:10.1007/s10545-010-9237-9. PMC 3091031. PMID 21103937.
  19. ^ Lee DS, Flachsová E, Bodnárová M, Demeler B, Martásek P, Raman CS (October 2005). "Structural basis of hereditary coproporphyria". Proceedings of the National Academy of Sciences of the United States of America. 102 (40): 14232–7. doi:10.1073/pnas.0506557102. PMC 1224704. PMID 16176984.
  20. ^ Schmitt C, Gouya L, Malonova E, Lamoril J, Camadro JM, Flamme M, Rose C, Lyoumi S, Da Silva V, Boileau C, Grandchamp B, Beaumont C, Deybach JC, Puy H (October 2005). "Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria". Human Molecular Genetics. 14 (20): 3089–98. doi:10.1093/hmg/ddi342. PMID 16159891.
  21. ^ Heyer NJ, Bittner AC, Echeverria D, Woods JS (February 2006). "A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production". Toxicology Letters. 161 (2): 159–66. doi:10.1016/j.toxlet.2005.09.005. PMID 16214298.

Further reading

Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

External links

This article incorporates text from the public domain Pfam and InterPro: IPR001260

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Coproporphyrinogen III oxidase Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001260

Coprogen oxidase (i.e. coproporphyrin III oxidase or coproporphyrinogenase) catalyses the oxidative decarboxylation of coproporphyrinogen III to proto-porhyrinogen IX in the haem and chlorophyll biosynthetic pathways [ PUBMED:8407975 , PUBMED:8219054 ]. The protein is a homodimer containing two internally bound iron atoms per molecule of native protein [ PUBMED:3516695 ]. 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 240
Number in full: 5226
Average length of the domain: 284.60 aa
Average identity of full alignment: 46 %
Average coverage of the sequence by the domain: 88.14 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 31.8 31.8
Trusted cut-off 31.8 32.9
Noise cut-off 31.2 31.2
Model length: 303
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Coprogen_oxidas domain has been found. There are 26 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

Loading structure mapping...