Any feedback?
No. of entries
Information on EC 3.5.2.17 - hydroxyisourate hydrolase
for references in articles please use BRENDA:EC3.5.2.17
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 3 Hydrolases
3.5 Acting on carbon-nitrogen bonds, other than peptide bonds
3.5.2 In cyclic amides
3.5.2.17 hydroxyisourate hydrolase
IUBMB Comments
The reaction is the first stage in the conversion of 5-hydroxyisourate into S-allantoin. This reaction will also occur spontaneously but more slowly.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
- 3.5.2.17
- amyloidosis
-
amyloid
- polyneuropathy
- cardiac
-
fibril
- hereditary
- cardiomyopathy
-
amyloidogenic
- neuropathy
- thyroxin
- albumin
- retinol
- tetramer
- nerve
-
retinol-binding
-
apolipoproteins
-
senile
- alzheimer
- immunoglobulin
-
cerebrospinal
- misfolding
- plexus
-
scintigraphy
- ventricular
- choroid
- transferrin
-
vitreous
- haptoglobin
-
congo
-
carpal
-
amyloidogenesis
-
echocardiography
- malnutrition
-
late-onset
-
prealbumin
-
ejection
- light-chain
- csf
-
endomyocardial
- medicine
-
fibrillogenesis
-
homotetrameric
- leptomeningeal
- gammopathy
-
sensorimotor
-
deiodinase
-
orthostatic
-
sural
- dysautonomia
-
non-amyloidogenic
-
portuguese
Synonyms
transthyretin, transthyretin-like protein, hydroxyisourate hydrolase, hiuhase, 5-hydroxyisourate hydrolase, transthyretin-related protein, hiuase, hiu hydrolase, sbttr, ectrp, more
top
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5-hydroxyisourate hydrolase
HIU
HIUHase
hydroxyisourate hydrolase
transthyretin
transthyretin-related protein
5-hydroxyisourate hydrolase
-
-
-
-
HIUHase
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-hydroxyisourate + H2O = 5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
The reaction is the first stage in the conversion of 5-hydroxyisourate into S-allantoin. This reaction will also occur spontaneously but more slowly
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
urate conversion to allantoin I, urate conversion to allantoin II, urate conversion to allantoin III
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
5-hydroxyisourate amidohydrolase
The reaction is the first stage in the conversion of 5-hydroxyisourate into S-allantoin. This reaction will also occur spontaneously but more slowly.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
255885-20-2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-hydroxyisourate + H2O
2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: enzyme shows 5-hydroxyisourate hydrolase and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase activities in vitro
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: ureide pathway
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: reaction is likely to be initiated by a water molecule that is first activated by deprotonation. The hydrogen-bonding interactions between the water molecule and residues His7 and His92 would serve to orient the water ideally for attack at C6 of the purine ring. The C-terminal serine residue, Ser108, is in position to form a hydrogen bond to His7 and may indirectly participate in catalysis by inductively activating this residue. Deprotonation of the water by His7 creates a hydroxide nucleophile that attacks C6 of the purine ring, leading to a tetrahedral oxyanion intermediate. The charge on the resulting oxyanion would be stabilized by the positively charged guanidinium group of Arg41. Arg41 from the neighboring chain helps to stabilize the charge on the oxyanion intermediate.Collapse of the oxyanion would then lead to ring opening, with the final proton coming from the nearby Arg41. The original proton abstracted from a water molecule by His7 would then be transferred to Arg41 to complete the catalytic cycle
Products: -
Products: -
?
additional information
?
-
-
Substrates: reaction is likely to be initiated by a water molecule that is first activated by deprotonation. The hydrogen-bonding interactions between the water molecule and residues His7 and His92 would serve to orient the water ideally for attack at C6 of the purine ring. The C-terminal serine residue, Ser108, is in position to form a hydrogen bond to His7 and may indirectly participate in catalysis by inductively activating this residue. Deprotonation of the water by His7 creates a hydroxide nucleophile that attacks C6 of the purine ring, leading to a tetrahedral oxyanion intermediate. The charge on the resulting oxyanion would be stabilized by the positively charged guanidinium group of Arg41. Arg41 from the neighboring chain helps to stabilize the charge on the oxyanion intermediate.Collapse of the oxyanion would then lead to ring opening, with the final proton coming from the nearby Arg41. The original proton abstracted from a water molecule by His7 would then be transferred to Arg41 to complete the catalytic cycle
Products: -
Products: -
?
additional information
?
-
Substrates: reaction is likely to be initiated by a water molecule that is first activated by deprotonation. The hydrogen-bonding interactions between the water molecule and residues His7 and His92 would serve to orient the water ideally for attack at C6 of the purine ring. The C-terminal serine residue, Ser108, is in position to form a hydrogen bond to His7 and may indirectly participate in catalysis by inductively activating this residue. Deprotonation of the water by His7 creates a hydroxide nucleophile that attacks C6 of the purine ring, leading to a tetrahedral oxyanion intermediate. The charge on the resulting oxyanion would be stabilized by the positively charged guanidinium group of Arg41. Arg41 from the neighboring chain helps to stabilize the charge on the oxyanion intermediate.Collapse of the oxyanion would then lead to ring opening, with the final proton coming from the nearby Arg41. The original proton abstracted from a water molecule by His7 would then be transferred to Arg41 to complete the catalytic cycle
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
-
Substrates: ureide pathway
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
5-hydroxyisourate + H2O
5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylate
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme is not affected by 1 mM of Cr3+, Mg2+, or Ca2+
additional information
-
the enzyme is not affected by 1 mM of Cr3+, Mg2+, or Ca2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
addition of 3His to the N-terminal end weakens 5-hydroxyisourate hydrolysis activity, whereas it enhanced T3-binding activity of R54E/Y119T mutsant enzyme
-
additional information
addition of 3His to the N-terminal end weakens 5-hydroxyisourate hydrolysis activity, whereas it enhanced T3-binding activity of R54E/Y119T mutsant enzyme
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
5-hydroxyisourate
pH 7.5, 37Ā°C, recombinant enzyme lacking the signal peptide
0.093
5-hydroxyisourate
mutant S108A, pH 7.6, temperature not specified in the publication
0.103
5-hydroxyisourate
wild-type, pH 7.6, temperature not specified in the publication
0.195
5-hydroxyisourate
mutant R41K, pH 7.6, temperature not specified in the publication
0.43
5-hydroxyisourate
mutant H92N, pH 7.6, temperature not specified in the publication
4.4
5-hydroxyisourate
mutant H7N, pH 7.6, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.35
5-hydroxyisourate
mutant H92N, pH 7.6, temperature not specified in the publication
0.8
5-hydroxyisourate
mutant H7N, pH 7.6, temperature not specified in the publication
24
5-hydroxyisourate
pH 7.5, 37Ā°C, recombinant enzyme lacking the signal peptide
34.7
5-hydroxyisourate
mutant R41K, pH 7.6, temperature not specified in the publication
81
5-hydroxyisourate
mutant S108A, pH 7.6, temperature not specified in the publication
172
5-hydroxyisourate
wild-type, pH 7.6, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.18
5-hydroxyisourate
mutant H7N, pH 7.6, temperature not specified in the publication
0.82
5-hydroxyisourate
mutant H92N, pH 7.6, temperature not specified in the publication
180
5-hydroxyisourate
mutant R41K, pH 7.6, temperature not specified in the publication
870
5-hydroxyisourate
mutant S108A, pH 7.6, temperature not specified in the publication
1700
5-hydroxyisourate
wild-type, pH 7.6, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
-
point mutation Y98Cin the gene encoding mouse HIU hydrolase, Urah, results in undetectable protein expression. Mice homozygous for this mutation develop elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also develop hepatocellular carcinoma, and tumor development is accelerated by exposure to radiation
evolution
the enzyme belongs to the 5-hydroxyisourate hydrolase/transthyretin superfamily: evolutionary and functional analyses, overview. Teleosts have highly diverged genomes that resulted from whole genome duplication, which leads to an extensive diversity of paralogous genes. Transthyretin, an extracellular thyroid hormone binding protein, is thought to have evolved from an ancestral 5-hydroxyisourate hydrolase by gene duplication at some stage of chordate evolution. Phylogenetic analysis of the teleost aa sequences reveals the presence of two HIUHase subfamilies, HIUHase 1 (which has an N-terminal peroxisomal targeting signal-2) and HIUHase 2 (which does not have an N-terminal PTS2), and one transthyretin family
evolution
evolution of transthyretin from 5-hydroxyisourate hydrolase to triiodothyronine distributor to thyroxine distributor
evolution
sequential molecular events of functional trade-offs in 5-hydroxyisourate hydrolase before and after gene duplication led to the evolution of transthyretin during chordate diversification
evolution
sequential molecular events of functional trade-offs in 5-hydroxyisourate hydrolase before and after gene duplication led to the evolution of transthyretin during chordate diversification
metabolism
the enzyme catalyzes the hydrolysis of 5-hydroxyisourate in the purine degradation pathway, and transthyretin, a thyroid hormone binding protein
metabolism
the enzymes is involved in uric acid metabolism
Show AA Sequence and Transmembrane Helices (16050 entries)
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
12439
-
x * 12439, calculated, x * 15000, SDS-PAGE of recombinant protein
15000
-
x * 12439, calculated, x * 15000, SDS-PAGE of recombinant protein
68000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 12439, calculated, x * 15000, SDS-PAGE of recombinant protein
homotetramer
tetramer