2.5.1.61: hydroxymethylbilane synthase
This is an abbreviated version!
For detailed information about hydroxymethylbilane synthase, go to the full flat file.
Word Map on EC 2.5.1.61
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2.5.1.61
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porphyria
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intermittent
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heme
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aip
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erythrocyte
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delta-aminolevulinic
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5-aminolevulinic
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gapdh
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erythroid
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genorm
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urinary
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dehydratase
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protoporphyrin
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ferrochelatase
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normfinder
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housekeeping
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tetrapyrrole
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bestkeeper
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coproporphyrinogen
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neurovisceral
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ywhaz
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protoporphyrinogen
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pyrrole
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variegate
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photodynamic
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erythroid-specific
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half-normal
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porphyrinogenic
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coproporphyria
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hematin
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proto
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tarda
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pharmacology
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beta-2-microglobulin
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hyponatremia
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diagnostics
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gata-1
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medicine
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rpl13a
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lightcycler
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cutanea
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beta-globin
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non-erythroid
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reffinder
- 2.5.1.61
- porphyria
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intermittent
- heme
- aip
- erythrocyte
-
delta-aminolevulinic
-
5-aminolevulinic
- gapdh
-
erythroid
-
genorm
- urinary
- dehydratase
- protoporphyrin
-
ferrochelatase
-
normfinder
-
housekeeping
- tetrapyrrole
-
bestkeeper
- coproporphyrinogen
-
neurovisceral
-
ywhaz
- protoporphyrinogen
- pyrrole
- variegate
-
photodynamic
-
erythroid-specific
-
half-normal
-
porphyrinogenic
- coproporphyria
- hematin
-
proto
- tarda
- pharmacology
-
beta-2-microglobulin
- hyponatremia
- diagnostics
-
gata-1
- medicine
-
rpl13a
-
lightcycler
-
cutanea
- beta-globin
-
non-erythroid
-
reffinder
Reaction
4 porphobilinogen
+
Synonyms
(HMB)-synthase, AN0121.3, EC 4.3.1.8, HemC, hepatic porphobilinogen deaminase, HMB synthase, HMB-S, HMBS, HMBS1a-synthase, HMBS1b-synthase, HMBS2a-synthase, HMBS2b-synthase, human non-erythropoietic PBGD isoform, human PBGD, human porphobilinogen deaminase, hydroxymethylbilane synthase, More, PBG deaminase, PBG-D, PBG-deaminase, PBGD, PGB-D, porphobilinogen ammonia-lyase (polymerizing), porphobilinogen deaminase, pre-uroporphyrinogen synthase, preuroporphyrinogen synthase, preuroporphyrinogen synthetase, synthase, uroporphyrinogen I, uPBGD, UPGI-S, URO-S, urogenI synthase, uroporphyrinogen I synthase, uroporphyrinogen I synthetase, uroporphyrinogen synthase, uroporphyrinogen synthetase
ECTree
2.5.1.61 hydroxymethylbilane synthaseAdvanced search results
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results (Engineering
Engineering on EC 2.5.1.61 - hydroxymethylbilane synthase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
K55Q/K59Q
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K55Q-K59Q mutant, lower specific activity than the wild-type enzyme
A84T
type OregonAR (c250G>A), autosomal recessive, therefore phenotype is homozygous, about 35% wild type activity
L64S
c.189dupT mutant type Saskatchewan with duplication that leads to a frameshift and thus to a trunkated enzyme due to a premature stop codon 65 and the exchange L64S, autosomal dominant
R149W
type Missouris (c.445C>T), substitution identical to human mutation but there leading to an nonsense mutation, autosomal dominant, less than 1% wild type activity
887insA
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site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
A226P
D99G
E250D
G748A
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site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
G748C
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site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
K132N
site-directed mutagenesis, the mutant shows no conformational or kinetic defect, no loss in relative activity (97% of wild-type activity) at standard conditions nor change in Vmax and Km. The mutation is not associated to acute intermittent porphyria, AIP
Q204K
c.610C>A, exon 10, missense mutation, 46% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R116W
site-directed mutagenesis, the mutant shows 0.5% of wild-type activity and defects in conformational stability. The mutation is associated to acute intermittent porphyria, AIP
R149Q
R149X
identification of a nonsense mutation in the PBGD gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria, phenotype, overview
R167Q
R167W
R173Q
R173Q/Q204K
R173Q is more severe with a resulting enzyme activity of nearly zero, the Q204K increases the negative effect, particularly on the protein stability, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R173W
R26C
R26H
R73Q/Q204K
a complex monoallelic mutation c.[518G>A; c.610C>A] (p.[Arg173Gln;p.Gln204Lys])
T59I
V215E
site-directed mutagenesis, the mutant shows 30% of wild-type activity and lower conformational stability and probably a perturbed elongation process, also 70% loss in both activity and Vmax. The mutation is associated to acute intermittent porphyria, AIP
L116K
the specific activity of this recombinant mutant enzyme is 5fold higher than that of the recombinant wild type enzyme, catalyzes the formation of uroporphyrinogen I in addition to uroporphyrinogen III
D44A
specific activity is only about 2% of that of the wild type enzyme
Q200L
mutant lacks the dipyrromethane cofactor and completely loses the catalytic activity
additional information
A226P
c.675delA, exon 12, 0.05% wild type activity, small deletion leads to stop codon after 28 completely different amino acids compared to wild type, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
D99G
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site-directed mutagenesis, inactive holo-enzyme mutant existing as a complex with 2 substrate molecules covalently bound to the dipyrromethane cofactor
E250D
c.750A>T, exon 12, missense mutation, 0.5% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R149Q
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site-directed mutagenesis, inactive apo-enzyme which is unable to assemble with the dipyrromethane cofactor, the mutant enzyme is unstable and heat-labile
R167Q
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site-directed mutagenesis, mutation of active site residue, highly reduced activity compared to the wild-type enzyme, formation of stable enzyme-intermediate complexes
R167Q
8.5% activity, reduced pH optimum from 8.0 to 6.0, accumulates long-lived intermediate complexes
R167W
site-directed mutagenesis, the mutant shows 4.2% of wild-type activity and defects in enzyme kinetics associated with a very high Km and decreased Vmax. The mutation is associated to acute intermittent porphyria, AIP
R173Q
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site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, the major part of the enzyme exists as apo-enzyme without assembled dipyrromethane cofactor
R173Q
c.518G>A, exon 10, missense mutation, 0.15% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R173W
site-directed mutagenesis, the mutant shows 0.6% of wild-type activity and defects in conformational stability and in enzyme kinetics. The mutation is associated to acute intermittent porphyria, AIP
R26C
c.76C>T, exon 3, 0.3% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R26H
c.77G>A, exon 3, 0.2% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
additional information
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all, six, methionine residues are replaced by SeMet
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
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4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, accumulation of substrates, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
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4 distinct mutations cause acute intermittent porphyria in cats, mutant phenotype has brownish discolored teeth and brownish urine, both fluorescent under UV light, mutations affect housekeeping and erythroid-specific isozymes in the same way
additional information
type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
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type Massachusetts, in-frame 3 bp deletion (c.842_844delGAG = delGly281), autosomal dominant, less than 1% wild type activity
additional information
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analysis of naturally occurring mutations causing acute intermittent porphyria, e.g. recurrent mutations G111R and R173Q occurring at CpG motifs from different patients, countries of origin, overview, haplotype analysis, polymorphism analysis, microsatellite marker analysis, oerview
additional information
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the mutations of the enzyme cause acute intermittent porphyria
additional information
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identification of a mutation in the porphobilinogen deaminase gene in a Slovak acute intermittent porphyria patient, phenotype, the recombinantly expressed mutant enzyme shows 0.18% of wild-type activity, overview
additional information
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mutations involved in acute intermittent porphyria, AIP, lead to an inactivation of the mutant enzyme, the mutations influence the structure and function of the enzyme
additional information
disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
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disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
previously known mutations that are identified by molecular analysis of the hydroxymethylbilane synthase gene are c.76C>T (R26Cys), c.77G>A (R26H), c.518G>A (R173Q), c.771 + 1G>T (causing donor splice site defect, deletion of exon 12), novel mutations are c.610C>A (Q204K), c.675delA (A226P with stop codon 28), c.750A>T (E250D), one patient shows double mutation of R173Q and Q204K
additional information
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previously known mutations that are identified by molecular analysis of the hydroxymethylbilane synthase gene are c.76C>T (R26Cys), c.77G>A (R26H), c.518G>A (R173Q), c.771 + 1G>T (causing donor splice site defect, deletion of exon 12), novel mutations are c.610C>A (Q204K), c.675delA (A226P with stop codon 28), c.750A>T (E250D), one patient shows double mutation of R173Q and Q204K
additional information
the commonly known variations g.-64T/C (rs589925), g.3581A/G (rs17075), g.6479T/G (rs1131488), and g.7064C/A (rs1784304) are detected by the high-resolution melting method, and also the identified DNA alternations c.76C>T (p.Arg26Cys), c.77G>A (p.Arg26His), c.95G>C (p.Arg32Pro), c.176C>T (p.Thr59Ille), a complex monoallelic mutation c.[518G>A; c.610C>A] (p.[Arg173Gln;p.Gln204Lys]), c.675delA (p.Ala226ProfsX28), c.750A>T (p.Glu250Asp), c.771+1G>T (r.spl?), c.965_966insA (p.Asn322LysfsX36), and c.972_973insG (p.Arg325AlafsX33) can be identified, additionally the alterations g.2922T>G, g.3059G>A, g.3119T/G (rs1006195), c.70G>A (p.Gly24Ser), c.87+5G>T (r.spl?), c.[518G>A;c.610C>A] (p.[Arg173Gln, p.Gln204Lys]), g.7175A>G, c.899_900delinsTGCCTGCATCTG (p.His300LeuFsX10), g.7998G/A (rs1799997) are identified in 97 subjects
additional information
disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
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disruption in one allele and partial disruption of other allele lead to 25-30% activity compared to wild type
additional information
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4 insertion allels (m1-m4) of camouflage1 (cf1) mutant, mutant develops nonclonal, yellow-green sectors in leaves based on bundle sheath cell-specific death, yellow mutant regions show reduced levels of chlorophyll a + b, and total carotenoids, reduced photosynthesis and stomatal conductance compared to wild type and green regions of the mutant, constant light suppresses the cf1 sector formation, sectors only form during a limited time of leaf development, underlying is a decreased enzyme activity and increased levels of the substrate in green and yellow regions, yellow regions show an additional reduction in catalase activity
