Information on EC 3.5.1.92 - pantetheine hydrolase and Organism(s) Homo sapiens and UniProt Accession O95498

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UNIPROT: O95498
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The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.5.1.92
-
RECOMMENDED NAME
GeneOntology No.
pantetheine hydrolase
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme vanin-1 mutation N131S is associated with high blood pressure or hypertension via vanin-1 misfolding and degradation as the underlying molecular mechanism
metabolism
-
key enzyme linking metabolic disease and inflammation
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
pantetheine + H2O
pantothenic acid + cysteamine
show the reaction diagram
(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
-
-
-
-
?
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
-
-
based on LC-MS analysis, demonstrating that pantothenate-7-amido-4-methylcoumarin is hydrolyzed by vanin-1 at the amide-bond
-
?
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
pantetheine + H2O
pantothenic acid + cysteamine
show the reaction diagram
(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
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
-
i.e. RR6
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
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
dithiothreitol
-
vanin-1 activity is reduced in the absence of dithiothreitol and in the presence of a high level of 50 mM dithiothreitol
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
roscovitine
-
from library of pharmacologically active compounds, LOPAC
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytokine IL-17
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cytokine Th1
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additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13 - 28
pantothenate-7-amido-4-methylcoumarin
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, 25°C
0.00404
5-(N,N-Hexamethylene)amiloride
Homo sapiens;
-
pH 7.5, 25°C
0.0135
8-cyclopentyl-1,3-dipropylxanthine
Homo sapiens;
-
pH 7.5, 25°C
0.0095
beta-lapachone
Homo sapiens;
-
pH 7.5, 25°C
0.0079
N2-(cis-2-aminocyclohexyl)-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine hydrochloride
Homo sapiens;
-
pH 7.5, 25°C
0.0176
roscovitine
Homo sapiens;
-
pH 7.5, 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
-
-
7.5
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assay at
8
-
assay at
additional information
-
greatly reduced activity observed at both acidic (pH 3.0) and basic (pH 10.0) conditions
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
normal skin, psoriatic lesions, atopic dermatitis lesions
Manually annotated by BRENDA team
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peripheral blood leukocyte
Manually annotated by BRENDA team
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lung epithelial cells, transfected and selected for stable expression of human vanin-1
Manually annotated by BRENDA team
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normal skin, psoriatic lesions, atopic dermatitis lesions
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
membrane-bound
Manually annotated by BRENDA team
-
a glycosylphosphatidylinositol (GPI)-anchored ectoenzyme
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
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
-
-
-
-
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54000
-
size exclusion chromatography-multiangular light scattering (SEC-MALS)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oligomer
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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
-
a glycosylphosphatidylinositol (GPI)-anchored ectoenzyme
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, 25°C, 40-50 days, or 4 weeks after microseeding, X-ray diffraction structure determination and analysis at 2.25 A resolution, molecular replacement and modeling
-
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
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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
-
stable expression of vanin-1 in HEK-293 cells
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transient expression of soluble FLAG-tagged truncated enzyme mutant, and mutant enzymes E249Q and E439Q in HEK-293T cells
-
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
-
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
-
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
-
construction of a truncated mutant comprising amino acids 22-493, deleting the native signal sequence and the C-terminal GPI-anchor sequence, and cloning downstream of the mouse interleukin-3 signal peptide in the mammalian expression vector pAPEX-3P and a FLAG tag DYDDDDK
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
-
vanin-1 is a potential biomarker for nephrotoxicant-induced renal injury