Information on EC 3.5.1.92 - pantetheine hydrolase

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY hide
3.5.1.92
-
RECOMMENDED NAME
GeneOntology No.
pantetheine hydrolase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(R)-pantetheine + H2O = (R)-pantothenate + 2-aminoethanethiol
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of amide bond
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Pantothenate and CoA biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
(R)-pantetheine amidohydrolase
The enzyme hydrolyses only one of the amide bonds of pantetheine. The substrate analogues phosphopantetheine and CoA are not substrates. The enzyme recycles pantothenate (vitamin B5) and produces 2-aminoethanethiol (cysteamine), a potent anti-oxidant [5].
CAS REGISTRY NUMBER
COMMENTARY hide
56093-18-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
Bos taurus Holstein
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
key enzyme linking metabolic disease and inflammation
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
show the reaction diagram
(R)-pantetheine + H2O
(R)-pantothenate + cysteamine
show the reaction diagram
(R)-pantetheine 4-phosphate + H2O
?
show the reaction diagram
-
10% of the activity with (R)-pantetheine
-
-
?
(S)-ethyl pantetheine + H2O
?
show the reaction diagram
-
80% of the activity with (R)-pantetheine
-
-
?
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-octadecylphospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-octadecylphospho-1D-myo-inositol + acetate
show the reaction diagram
-
-
-
-
?
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-[1,2-bis(hexadecanoyl)-sn-glycero]phospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-[1,2-bis(hexadecanoyl)-sn-glycero]phospho-1D-myo-inositol + acetate
show the reaction diagram
-
-
-
-
?
N,N'-bis(pantothenyl)-1,6-diaminohexane + H2O
?
show the reaction diagram
-
96% of the activity with (R)-pantetheine
-
-
?
N-(4-methyl-2-oxo-2H-chromen-7-yl)-D-pantothenamide + H2O
(R)-pantothenate + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
pantetheine + H2O
pantothenate + cysteamine
show the reaction diagram
pantetheine + H2O
pantothenic acid + cysteamine
show the reaction diagram
pantothenate-7-amido-4-methylcoumarin + H2O
pantothenic acid + 7-amino-4-methylcoumarin
show the reaction diagram
pantothenyl-beta-aminoethanol + H2O
?
show the reaction diagram
S-ethylpantetheine + H2O
?
show the reaction diagram
-
-
-
-
?
S-pantetheine 3-pyruvate + H2O
S-cysteamine 3-pyruvate + pantothenate
show the reaction diagram
-
-
S-cysteamine 3-pyruvate spontaneously forms a cyclic product
-
?
S-pantetheine-3-pyruvate + H2O
S-cysteamine 3-pyruvate + pantothenate
show the reaction diagram
-
-
-
-
?
S-pantetheine-3-pyruvate + H2O
S-cysteamine-3-pyruvate + pantothenate
show the reaction diagram
-
-
S-cysteamine-3-pyruvate cyclizes in a non-rate-limiting step to give 2H-1,4-thiazin-5,6-dihydro-3-carboxylic acid, a compound exhibiting a strong absorption at 296 nm
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
show the reaction diagram
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-octadecylphospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-octadecylphospho-1D-myo-inositol + acetate
show the reaction diagram
-
-
-
-
?
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-[1,2-bis(hexadecanoyl)-sn-glycero]phospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-[1,2-bis(hexadecanoyl)-sn-glycero]phospho-1D-myo-inositol + acetate
show the reaction diagram
-
-
-
-
?
pantetheine + H2O
pantothenate + cysteamine
show the reaction diagram
pantetheine + H2O
pantothenic acid + cysteamine
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dithiothreitol
-
important for vanin-1 activity, vanin-1 activity is reduced in the absence of dithiothreitol and in the presence of a high level of 50 mM dithiothreitol. Optimal concentration: 0.4 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-2,4-dihydroxy-3,3-dimethyl-N-(3-oxo-4-phenylbutyl)butanamide
2,3-bis[(2-hydroxyethyl)thio]-1,4-naphthoquinone
-
i.e. NSC 95397, from library of pharmacologically active compounds, LOPAC
2-mercaptoethanol
-
reduced vanin-1 activity
2-Nitro-5-thiocyanobenzoate
-
0.1 mM, 15 min, 10% residual activity in absence of substrate S-pantetheine-3-pyruvate, 51% residual activity in presence of the substrate S-pantetheine-3-pyruvate
4,4'-dithiodipyridine
5,5'-dithiobis(2-nitrobenzoate)
-
0.1 mM, 15 min, 78% residual activity in absence of substrate S-pantetheine-3-pyruvate, 33% residual activity in presence of the substrate S-pantetheine-3-pyruvate
5-(N,N-Hexamethylene)amiloride
-
from library of pharmacologically active compounds, LOPAC
8-cyclopentyl-1,3-dipropylxanthine
-
from library of pharmacologically active compounds, LOPAC
beta-lapachone
-
from library of pharmacologically active compounds, LOPAC
Bromopyruvate
-
0.1 mM, 15 min, 2% residual activity in absence of substrate S-pantetheine-3-pyruvate, 76% residual activity in presence of the substrate S-pantetheine-3-pyruvate
cystamine
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0.1 mM, 15 min, 41% residual activity in absence of substrate S-pantetheine-3-pyruvate, 60% residual activity in presence of the substrate S-pantetheine-3-pyruvate
cysteamine
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5 mM, 55% inhibition
cystine
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5 mM, 15 min, 100% residual activity in absence of substrate S-pantetheine-3-pyruvate, 32% residual activity in presence of the substrate S-pantetheine-3-pyruvate
dithiothreitol
-
vanin-1 activity is reduced in the absence of dithiothreitol and in the presence of a high level of 50 mM dithiothreitol
GSSG
-
-
H2O2
-
0.1 mM, 15 min, 17% residual activity in absence of substrate S-pantetheine-3-pyruvate, 47% residual activity in presence of the substrate S-pantetheine-3-pyruvate
Hg2+
-
-
iodoacetamide
iodoacetate
mercaptoethanol
-
-
N2-(cis-2-aminocyclohexyl)-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine hydrochloride
-
i.e. CGP-74514A hydrochloride, from library of pharmacologically active compounds, LOPAC
NaAsO2
-
1 mM, 15 min, 90% residual activity in absence or presence of substrate S-pantetheine-3-pyruvate
NaN3
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15 mM, 90% inhibition
NEM
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1 mM, 15 min, no residual activity in absence of substrate S-pantetheine-3-pyruvate, 54% residual activity in presence of the substrate S-pantetheine-3-pyruvate
o-Iodosobenzoate
-
0.05 mM, 15 min, 15% residual activity in absence of substrate S-pantetheine-3-pyruvate, 53% residual activity in presence of the substrate S-pantetheine-3-pyruvate
p-aminophenylarsine oxide
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1 mM, 15 min, 45% residual activity in absence of substrate S-pantetheine-3-pyruvate, 55% residual activity in presence of the substrate S-pantetheine-3-pyruvate
pantethine
pantothenate
-
50 mM, 60% inhibition
PCMB
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0.0001 mM, 15 min, 1% residual activity in absence of substrate S-pantetheine-3-pyruvate, 68% residual activity in presence of the substrate S-pantetheine-3-pyruvate
Phenylarsine oxide
-
1 mM, 15 min, 48% residual activity in absence of substrate S-pantetheine-3-pyruvate, 52% residual activity in presence of the substrate S-pantetheine-3-pyruvate
roscovitine
-
from library of pharmacologically active compounds, LOPAC
additional information
-
no inhibition by 5 mM GSSG in absence or presence of substrate S-pantetheine-3-pyruvate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
activates
cytokine IL-17
increased expression of vanin-1; increased expression vanin-3
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cytokine Th1
increased expression of vanin-1; increased expression vanin-3
-
dithioerythritol
-
1-13 mM, activates
dithiothreitol
-
activates
additional information
19fold upregultion of gene expression of vanin-1 psoriasis, vanin-1 expression in atopic dermatits little increased; 2.3fold overexpression of vanin-3 in psioriais; induced expression of vanin-2 in psoriasis and atopic dermatitis; mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-1 in reconstructed human epidermis; mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-3 in reconstructed human epidermis
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
(R)-pantetheine
-
-
5
pantetheine
-
-
13 - 28
pantothenate-7-amido-4-methylcoumarin
0.000028
S-cysteamine-3-pyruvate
-
pH 7.6, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004
mercaptoethanol
-
-
0.0024 - 0.0035
pantethine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0057
2,3-bis[(2-hydroxyethyl)thio]-1,4-naphthoquinone
Homo sapiens
-
pH 7.5, 25C
0.00404
5-(N,N-Hexamethylene)amiloride
Homo sapiens
-
pH 7.5, 25C
0.0135
8-cyclopentyl-1,3-dipropylxanthine
Homo sapiens
-
pH 7.5, 25C
0.0095
beta-lapachone
Homo sapiens
-
pH 7.5, 25C
0.0079
N2-(cis-2-aminocyclohexyl)-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine hydrochloride
Homo sapiens
-
pH 7.5, 25C
0.0176
roscovitine
Homo sapiens
-
pH 7.5, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
a simple, rapid, very sensitive, and specific continous spectrophotometric assay of pantetheinase activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 5.5
-
-
6.5 - 8
-
-
7.5 - 8.5
-
-
7.5
-
assay at
8
-
assay at
9 - 9.5
-
-
additional information
-
greatly reduced activity observed at both acidic (pH 3.0) and basic (pH 10.0) conditions
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 9.7
-
pH 5.5: about 50% of maximal activity, pH 9.7: about 70% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
circulating
Manually annotated by BRENDA team
-
peripheral blood leukocyte
Manually annotated by BRENDA team
-
similar expression like in liver, determined by RT-PCR
Manually annotated by BRENDA team
-
lung epithelial cells, transfected and selected for stable expression of human vanin-1
Manually annotated by BRENDA team
normal skin, psoriatic lesions, atopic dermatitis lesions; normal skin, psoriatic lesions, atopic dermatitis lesions; normal skin, psoriatic lesions, atopic dermatitis lesions
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
-
-
Manually annotated by BRENDA team
-
an highly sensitive fluorescent assay using a novel fluorescent pantotheine derivative is used for characterization of a soluble version of human vanin-1 recombinant protein, identification of hits from high-throughput screening, and quantification of vanin pantotheinase acitivity in cell lines and tissues
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
-
ultracentrifugation
72000
-
-
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 60000, SDS-PAGE
oligomer
-
the residues important for oligomerization are Gln179-Phe182, Pro191-Glu193, Phe212-Asp218, Pro243-His251 and Leu326-Asn330
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycolipoprotein
glycoprotein
lipoprotein
-
a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant FLAG-tagged truncated enzyme, and enzyme mutants E249Q and E439Q, free and in complex with pantothenic acid or inhibitor RR6, sitting drop vapor diffusion method, mixing of 200 nl of 12 mg/ml kifunensine-treated vanin 1 protein in 50 mM bis-tris pH 6.5, 50 mM NaCl, with 200 nl of reservoir solution containing 21% w/v PEG 1500, 10% v/v malate-MES-Tris, pH 6.3, with or without 1 mM pantothenic acid or inhibitor RR6, 25C, 40-50 days, or 4 weeks after microseeding, X-ray diffraction structure determination and analysis at 2.25 A resolution, molecular replacement and modeling
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7.6
-
good stability, rapid decrease outside this range
659867
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
after solubilization, the enzsme can be stored indefinitely in the frozen state without significant loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 12 months without loss of activity
-
-20C, pH 7, several months without significant loss of activity
-
0C, dilute solutions lose 5% activity per week
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme,His- and Flag-tagged vanin-1 is purified over a 10 ml HisTrap Fast Flow column (a nickel affinity chromatography), 95% purity
-
recombinant soluble FLAG-tagged truncated enzyme mutant from 293 cells by immunoaffinity chromatography and gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in CHO cells
-
gene vnn1, real-time quantitative PCR enzyme expression analysis
-
gene VNN2, semiquantitative RT-PCR expression analysis in ovulatory follicles and granulosa cells, DNA-binding activity of bovine VNN2 promoter, overview
stable expression of vanin-1 in HEK-293 cells
-
transient expression of soluble FLAG-tagged truncated enzyme mutant, and mutant enzymes E249Q and E439Q in HEK-293T cells
-
vanin-1 is highly expressed in liver and is under transcriptional control of PPAR-alpha and nutritional statu
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
atenolol and diltiazem, two current drugs for treating hypertension, reduce the vanin-1 protein level
-
in lipopolysaccharide-treated cells, vanin-1 expression increases 5.1 to 40.2fold. In sodium arsenite-treated cells, vanin-1 expression increases 1.9 to 39.8fold
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mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
renal vanin-1 protein levels are significantly decreased in rats treated with the higher dose of cisplatin and gentamicin, and vanin-1 immunoreactivity in tubular cells is reduced through cisplatin
the mRNA expression of vanin-1 increases about 2.4fold after the exposure of renal tubular cells to organic solvents (allyl alcohol, ethylene glycol, formaldehyde, chloroform, and phenol) for 24 h
-
the mRNA level of vanin-1 significantly elevates in the renal cortices of ethylene glycol-exposed rats
-
VNN2 promoter activity and mRNA expression are inhibited by protein kinase A and ERK1/2 inhibitors
VNN2 promoter activity and mRNA expression are markedly stimulated by forskolin and overexpression of the catalytic subunit of protein kinase A
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E249Q
-
site-directed mutagenesis
E439Q
-
site-directed mutagenesis
E79A
-
site-directed mutagenesis
K178A
-
site-directed mutagenesis
N131S
-
naturally occuring mutation in both African Americans and Mexican Americans, the mutation is associated with significantly lower plasma vanin-1 protein levels, the N131S vanin-1 is subjected to rapid endoplasmic reticulum-associated degradation as the underlying mechanism for its reduction, N131S vanin-1 is degraded significantly faster than wild type vanin-1 greatly reducing vanin-1 present on the plasma membrane and pantetheinase activity, overview
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
drug development
-
the highly sensitive fluorescent assay for the hydrolysis of pantothenate-7-amido-4-methylcoumarin as substrate to pantothenic acid and 7-amino-4-methylcoumarin could be a powerful tool for target validation and drug lead identification and characterization
medicine