1.3.3.3: coproporphyrinogen oxidase
This is an abbreviated version!
For detailed information about coproporphyrinogen oxidase, go to the full flat file.
Word Map on EC 1.3.3.3
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1.3.3.3
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heme
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protoporphyrinogen
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coproporphyria
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protoporphyrin
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porphyria
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ferrochelatase
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uroporphyrinogen
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5-aminolevulinic
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porphobilinogen
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tetrapyrrole
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porphyrinogens
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medicine
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oxygen-independent
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coproporphyrinuria
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mg-protoporphyrin
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ala-pdt
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delta-aminolaevulinic
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uroporphyrin
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cutanea
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analysis
- 1.3.3.3
- heme
- protoporphyrinogen
- coproporphyria
- protoporphyrin
- porphyria
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ferrochelatase
- uroporphyrinogen
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5-aminolevulinic
- porphobilinogen
- tetrapyrrole
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porphyrinogens
- medicine
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oxygen-independent
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coproporphyrinuria
- mg-protoporphyrin
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ala-pdt
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delta-aminolaevulinic
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uroporphyrin
-
cutanea
- analysis
Reaction
Synonyms
copro'gen oxidase, Coprogen oxidase, coproporphyinogen oxidase, coproporphyrinogen III oxidase, coproporphyrinogen oxidase, coproporphyrinogen-III oxidase, coproporphyrinogenase, COX, CPgen oxidase, CPGox, CPO, CPO III oxidase, CPOX, CPOX4, CPX, CPX1, CPX2, HEM13, Hem13p, HemF, HEMN1, KlHEM13, LIN2, LMM2, O2-dependent coproporphyrinogen III oxidase, oxygen-dependent coproporphyrinogen III oxidase, oxygen-dependent coproporphyrinogen-III oxidase, Sll1185
ECTree
1.3.3.3 coproporphyrinogen oxidaseAdvanced search results
results (
results (Engineering
Engineering on EC 1.3.3.3 - coproporphyrinogen oxidase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C167S
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site-directed mutagenesis, activity and kinetics similar to the wild-type
G127V
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site-directed mutagenesis, activity and kinetics similar to the wild-type
P133A
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site-directed mutagenesis, activity and kinetics similar to the wild-type
T132A
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site-directed mutagenesis, activity and kinetics similar to the wild-type
W123L
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site-directed mutagenesis, activity and kinetics similar to the wild-type
W124R
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site-directed mutagenesis, activity and kinetics similar to the wild-type
W166L
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site-directed mutagenesis, activity and kinetics similar to the wild-type
W298L
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site-directed mutagenesis, activity and kinetics similar to the wild-type
W36L
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site-directed mutagenesis, activity and kinetics similar to the wild-type
Y160F
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site-directed mutagenesis, activity and kinetics similar to the wild-type
Y170F
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site-directed mutagenesis, activity and kinetics similar to the wild-type
Y213F
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site-directed mutagenesis, activity and kinetics similar to the wild-type
Y240F
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site-directed mutagenesis, activity and kinetics similar to the wild-type
Y276F
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site-directed mutagenesis, activity and kinetics similar to the wild-type
A203T
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natural mutation due to single nucleotide substitution 607G>A, identified in a patient with hereditary coproporphyria
C991T/C1339T
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identification of 2 coexisting mutations, C991T and C1339T, on a single allele in the enzyme' gene in Swedish patients with hereditary coproporphyria, biochemical analysis of the patients carrying the mutations, overview
D400A
D400R
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less than 1% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
F395G
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4% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
F405G
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1% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
G188W
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a naturally occuring frameshift mutation p.Gly188TrpfsX45 in hereditary coproporphyria patient from Italian population, phenotype, overview
G242C
G279R
novel nucleotide transition found, is unstable, and produces ca. 2-5% of activity compared with the wild-type CPO
G402A
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less than 1% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
H148A
retains 39% of wild type enzyme activity for the overall conversion of coproporphyrinogen-III to protoporphyrinogen-IX
H158A
the mutant exhibits approximately 50fold lower activity than wild type recombinant CPO for the conversion of coproporphyrinogen-III to protoporphyrinogen-IX
H197A
the mutant exhibits approximately 50fold lower activity for the overall conversion of coproporphyrinogen-III to protoporphyrinogen-IX than wild type recombinant CPO, but the second oxidative decarboxylation step is not impaired, with mutant enzyme H197A retaining 100% of the wild type activity using harderoporphyrinogen as substrate
H227A
catalyzes the conversion of coproporphyrinogen-III to protoporphyrinogen-IX at a rate almost 2fold that of the wild type enzyme
K404E
K404H
site-directed mutagenesis, the mutant produces a high level of harderoporphyrinogen with low production of protoporphyrinogen similar to mutant K404E
K404N
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61% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
K404Q
site-directed mutagenesis, the mutant shows unaltered activity compared to the wild-type enzyme
L288W
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the mutation is associated with hereditary coproporphyria with posterior reversible encephalopathy
L398P
N272H
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natural polymorphism, twofold decrease in affinity for coproporphyrinogen-III. Specific activity in liver samples is 40-50% lower than in wild-type
R262A
R401A
R401D
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45% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
R401K
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63% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
R401W
S245F
T403N
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31% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
Y399L
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81% of residual activity compared with wild-type CPO, shows accumulation of coproporphyrinogen
H158A
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complete loss of activity, decreased stability, no copper content
additional information
D400A
impaired catalytic ability, with 0.047% of wild-type total product efficiency
D400A
the mutant produces no divinyl product, the Km value for coproporphyrinogen-III does not change significantly compared to the wild-type enzyme
D400A
the mutation impairs the catalytic ability of CPO relative to the wild type enzyme, not able to form divinyl products, but the Km value for coproporphyrinogen-III does not change significantly compared to the wild-type enzyme
D400A
site-directed mutagenesis, the inactive mutant D400A remains in a monomeric form
D400A
mutation severely impaires the catalytic activity, mutant performs, on average, less than a single turnover
G242C
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natural mutation due to single nucleotide substitution 724G>T, identified in a patient with hereditary coproporphyria
G242C
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a naturally occuring missense mutation in hereditary coproporphyria patient from Italian population, phenotype, overview
K404E
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66% of residual activity compared with wild-type CPO, causes substantial accumulation of harderoporphyrinogen
K404E
a naturally occuring mutant derived from patients with harderoporphyria, the mutant produces less harderoporphyrinogen. The K404E mutation leads to diminishment of the second step of the decarboxylation reaction during the conversion of coproporphyrinogen to protoporphyrinogen. The mutant enzyme forms dimers
L398P
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natural mutation due to single nucleotide substitution 1193T>C, identified in a patient with hereditary coproporphyria
L398P
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a naturally occuring missense mutation in hereditary coproporphyria patient from Italian population, phenotype, overview
R262A
impaired catalytic ability, with 0.00036% of wild-type total product efficiency
R262A
poor catalyst for the production of a divinyl product with a catalytic efficiency less than 0.01% compared to wild-type, including a 15fold higher Km for coproporphyrinogen-III
R262A
the mutant CPO is a poor catalyst for the production of a divinyl product, with a catalytic efficiency less than 0.01% compared to the wild type enzyme including a 15fold higher Km for coproporphyrinogen-III
R262A
mutation results in decreased kcat values and increased Km values. No product formation is detected with sunstrate mesoporphyrogen-VI
R401A
impaired catalytic ability, with 44% of wild-type total product efficiency
R401A
the efficiency of divinyl product formation for mutant enzyme R401A is about 3% compared to wild type CPO, with a 3fold increase in the Km value for coproporphyrinogen-III
R401A
the efficiency of divinyl product formation is about 3% compared to the wild type enzyme
R401A
mutation results in decreased kcat values and increased Km values. The mutant is able to convert mesoporphyrogen-VI to monovinyl product, although over 10fold less efficiently than wild-type
R401W
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75% of residual activity compared with wild-type CPO, causes substantial accumulation of harderoporphyrinogen
S245F
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natural mutation due to single nucleotide substitution 734C>T, identified in a patient with hereditary coproporphyria
S245F
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a naturally occuring missense mutation in hereditary coproporphyria patient from Italian population, phenotype, overview
additional information
spontaneous lesion formation mutant lin2-2
additional information
construction of a hemF and hemH deletion plasmids by transforming the linearized disruption vectors pDELTAhemF and pDELTAhemH into strain AB4.1, strain N402 genomic DNA is used as a template. Deletion of hemF (CPO) or hemH (FC) is conditionally lethal, and despite supplementation of hemin, DELTAhemF and DELTAhemH strains are still extremely impaired in growth. Co-overexpression of hemH, hemF, and the aminolevulinic acid synthase encoding hemA, increases the cellular accumulation of porphyrin intermediates suggesting regulatory mechanisms operating in the final steps of the fungal heme biosynthesis pathway. Gene hemF deletion strain displays a specific pigmented phenotype due to coproporphyrinogen III accumulation. Phenotypes, overview
additional information
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construction of a hemF and hemH deletion plasmids by transforming the linearized disruption vectors pDELTAhemF and pDELTAhemH into strain AB4.1, strain N402 genomic DNA is used as a template. Deletion of hemF (CPO) or hemH (FC) is conditionally lethal, and despite supplementation of hemin, DELTAhemF and DELTAhemH strains are still extremely impaired in growth. Co-overexpression of hemH, hemF, and the aminolevulinic acid synthase encoding hemA, increases the cellular accumulation of porphyrin intermediates suggesting regulatory mechanisms operating in the final steps of the fungal heme biosynthesis pathway. Gene hemF deletion strain displays a specific pigmented phenotype due to coproporphyrinogen III accumulation. Phenotypes, overview
additional information
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construction of a hemF and hemH deletion plasmids by transforming the linearized disruption vectors pDELTAhemF and pDELTAhemH into strain AB4.1, strain N402 genomic DNA is used as a template. Deletion of hemF (CPO) or hemH (FC) is conditionally lethal, and despite supplementation of hemin, DELTAhemF and DELTAhemH strains are still extremely impaired in growth. Co-overexpression of hemH, hemF, and the aminolevulinic acid synthase encoding hemA, increases the cellular accumulation of porphyrin intermediates suggesting regulatory mechanisms operating in the final steps of the fungal heme biosynthesis pathway. Gene hemF deletion strain displays a specific pigmented phenotype due to coproporphyrinogen III accumulation. Phenotypes, overview
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additional information
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HemF- mutant strain, unable to grow under aerobic condition
additional information
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18-somite stage cloche homozygous mutant embryos, development of hematopoietic and endothelial lineages is severely impaired, cpo is downregulated
additional information
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knockdown of zebrafish CPO using anti-sense morpholinos leads to a significant suppression of hemoglobin production without apparent reduction of blood cells, injection of human CPO RNA, but not a mutant CPO RNA similar to a mutant responsible for a hereditary coproporphyria, restores hemoglobin production in the CPO-MO-injected embryos, expression of CPO in the ICM is severely suppressed in both vlad tepes/gata1 mutants and in biklf-MO-injected embryos
additional information
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mutation of the nucleotide binding motif GGGXXTP does not affect the enzyme activity
additional information
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a duplication of a T in position 561 of the coding sequence, i.e.561dupT in exon 2 results in a frameshift that gives rise to a stop codon 45 residues downstream Glycine at position 188, i.e. p.Gly188TrpfsX45. Mutation identified in a patient with hereditary coproporphyria
additional information
enzyme engineering of mutant homodimer and heterodimer of coproporphyinogen oxidase. The His-tagged mutant enzyme forms a heterodimer in association with the HA-tagged wild-type enzyme, The monomeric form of mutated CPOX does not show any activity and homodimeric enzymes derived from hereditary coproporphyria (HCP) mutant show low activity (about 20% of the control). The chimeric heterodimers with wild-type and mutated subunits from HCP patients show low protoporphyrinogen producing activity. Some mutations of amino acids 401-404 are associated with marked accumulation of reaction intermediate harderoporphyrinogen, with a decrease in the production of protoporphyrinogen, whereas K404E derived from patients with harderoporphyria produces less harderoporphyrinogen. Functional analysis of heterodimer of mutant/wild-type complex, heterophilic forms of His-R388W/HA-wild-type, His-R391W/HA-wild-type, His-D400A/HA-wild-type, His-R401W/HA-wild-type, His-G402D/HA-wild-type and His-K404E/HA-wild-type, overview
additional information
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enzyme engineering of mutant homodimer and heterodimer of coproporphyinogen oxidase. The His-tagged mutant enzyme forms a heterodimer in association with the HA-tagged wild-type enzyme, The monomeric form of mutated CPOX does not show any activity and homodimeric enzymes derived from hereditary coproporphyria (HCP) mutant show low activity (about 20% of the control). The chimeric heterodimers with wild-type and mutated subunits from HCP patients show low protoporphyrinogen producing activity. Some mutations of amino acids 401-404 are associated with marked accumulation of reaction intermediate harderoporphyrinogen, with a decrease in the production of protoporphyrinogen, whereas K404E derived from patients with harderoporphyria produces less harderoporphyrinogen. Functional analysis of heterodimer of mutant/wild-type complex, heterophilic forms of His-R388W/HA-wild-type, His-R391W/HA-wild-type, His-D400A/HA-wild-type, His-R401W/HA-wild-type, His-G402D/HA-wild-type and His-K404E/HA-wild-type, overview
additional information
loss of inducibility due to the promoter mutations occur reproducibly with all C/EBP isoforms, arguing that CPO promoter activity depends upon C/EBP site location, and not simply upon inherent binding affinity, hypothetical modeling, overview
additional information
loss of inducibility due to the promoter mutations occur reproducibly with all C/EBP isoforms, arguing that CPO promoter activity depends upon C/EBP site location, and not simply upon inherent binding affinity, hypothetical modeling, overview
additional information
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loss of inducibility due to the promoter mutations occur reproducibly with all C/EBP isoforms, arguing that CPO promoter activity depends upon C/EBP site location, and not simply upon inherent binding affinity, hypothetical modeling, overview
additional information
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identification of diverse deleterious enzyme mutations in hereditary coproporphyria, structural effects of mutations, overview
additional information
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construction of enzyme-deficient DELTA sll1185 mutant, which fails to grow under aerobic conditions, with accumulation of coproporphyrin III. This growth defect is restored by cultivation under micro-oxic conditions
additional information
construction of enzyme-deficient DELTA sll1185 mutant, which fails to grow under aerobic conditions, with accumulation of coproporphyrin III. This growth defect is restored by cultivation under micro-oxic conditions
additional information
seedlings homozygous for a null mutation in the cpx1 gene completely lack chlorophyll and develop necrotic lesions in the light
additional information
seedlings homozygous for a null mutation in the cpx1 gene completely lack chlorophyll and develop necrotic lesions in the light
