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Information on EC 3.5.1.92 - pantetheine hydrolase
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3.5.1.92 pantetheine hydrolaseIUBMB Comments
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 .
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Word Map
- 3.5.1.92
- cysteamine
-
pantothen
-
gpi-anchored
-
ectoenzyme
- pantothenamides
-
gelatinase-associated
-
walter
-
aminothiol
- pantethine
- biotinidase
-
julius
- medicine
- diagnostics
- drug development
The enzyme appears in viruses and cellular organisms
Synonyms
vanin-1, pantetheinase, gpi-80, vanin, pagel, vanin 1, pantetheinases, vanin-3, vanin-2, vascular noninflammatory molecule 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
pantetheinase
vanin 1
vanin-1
vanin-2
vanin-3
vascular non-inflammatory molecule-1
VNN-1
VNN1
VNN2
vanin-1
-
belongs to the nitrilase superfamily, which contains the invariant catalytic triad residues: glutamate, lysine, and cysteine
vanin-1
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(R)-pantetheine + H2O = (R)-pantothenate + 2-aminoethanethiol
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
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
56093-18-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(R)-pantetheine 4-phosphate + H2O
?
-
10% of the activity with (R)-pantetheine
-
-
?
2-(6-[[N-(2,4-dihydroxy-3,3-dimethylbutanoyl)-beta-alanyl]amino]-1,3-benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-5-carboxylic acid + H2O
2-(6-amino-1,3-benzothiazol-2-yl)-4,5-dihydro-1,3-thiazole-5-carboxylic acid + N-(2,4-dihydroxy-3,3-dimethylbutanoyl)-beta-alanine
design, synthesis, and biological examination of a highly sensitive bioluminogenic probe for pantetheinase with a limit of detection of 1.14 ng/ml. Validation of the probe for application to detect the endogenous pantetheinase activity, overview
-
-
ir
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-octadecylphospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-octadecylphospho-1D-myo-inositol + acetate
-
-
-
-
?
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
-
-
-
-
?
N,N'-bis(pantothenyl)-1,6-diaminohexane + H2O
?
-
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
-
-
-
?
S-pantetheine 3-pyruvate + H2O
S-cysteamine 3-pyruvate + pantothenate
-
-
S-cysteamine 3-pyruvate spontaneously forms a cyclic product
-
?
S-pantetheine-3-pyruvate + H2O
S-cysteamine-3-pyruvate + pantothenate
-
-
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
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
pantetheine + H2O
pantothenic acid + cysteamine
-
development of a highly sensitive fluorescent assay using a novel fluorescently labeled pantotheine derivative for high throughput screening for drug development and for quantification in various cell types and tissues
-
-
?
pantothenate-7-amido-4-methylcoumarin + H2O
pantothenic acid + 7-amino-4-methylcoumarin
-
-
based on LC-MS analysis, demonstrating that pantothenate-7-amido-4-methylcoumarin is hydrolyzed by vanin-1 at the amide-bond
-
?
pantothenate-7-amido-4-methylcoumarin + H2O
pantothenic acid + 7-amino-4-methylcoumarin
-
-
based on LC-MS analysis
-
?
pantothenyl-beta-aminoethanol + H2O
?
-
75% of the activity with (R)-pantetheine
-
-
?
additional information
?
-
-
membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. The enzyme might by involved in the regulation of some immune functions maybe in the context of the response to oxidative stress
-
-
?
additional information
?
-
-
the transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development. The sex- and cell-type-specific expression of vanin-1 in the developing mpouse gonad in vivo is required to provide an appropriate environment for male germ cell development
-
-
?
additional information
?
-
-
the vanin-1 gene is involved in testis development in mouse
-
-
?
additional information
?
-
-
vanin-1 is a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level
-
-
?
additional information
?
-
-
vanin-1 plays a role in thymic reconstitution following damage by irradiation
-
-
?
additional information
?
-
-
vanin-1 regulates late adhesion steps of thymus homing under physiological, noninflammatory conditions
-
-
?
additional information
?
-
-
vanin-1-/- mice are less susceptible to intestinal inflammation, either acute or chronic. Pantetheinase activity of vanin-1 is a major regulator of intestinal inflammation, acting through cysteamine release
-
-
?
additional information
?
-
-
vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection
-
-
?
additional information
?
-
-
vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes
-
-
?
additional information
?
-
-
vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/anf mesenchymal precursors and phosphate donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells
-
-
?
additional information
?
-
-
vanin-1, by antagonizing PPARgamma, licenses the production of inflammatory mediators by intestinal epithelial cells
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
6-O-[N-acetyl-alpha-D-glucosaminyl]-1-octadecylphospho-1D-myo-inositol + H2O
6-O-alpha-D-glucosaminyl-1-octadecylphospho-1D-myo-inositol + acetate
-
-
-
-
?
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
-
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
(R)-pantetheine + H2O
(R)-pantothenate + 2-aminoethanethiol
-
-
-
?
additional information
?
-
-
membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. The enzyme might by involved in the regulation of some immune functions maybe in the context of the response to oxidative stress
-
-
?
additional information
?
-
-
the transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development. The sex- and cell-type-specific expression of vanin-1 in the developing mpouse gonad in vivo is required to provide an appropriate environment for male germ cell development
-
-
?
additional information
?
-
-
the vanin-1 gene is involved in testis development in mouse
-
-
?
additional information
?
-
-
vanin-1 is a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level
-
-
?
additional information
?
-
-
vanin-1 plays a role in thymic reconstitution following damage by irradiation
-
-
?
additional information
?
-
-
vanin-1 regulates late adhesion steps of thymus homing under physiological, noninflammatory conditions
-
-
?
additional information
?
-
-
vanin-1-/- mice are less susceptible to intestinal inflammation, either acute or chronic. Pantetheinase activity of vanin-1 is a major regulator of intestinal inflammation, acting through cysteamine release
-
-
?
additional information
?
-
-
vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection
-
-
?
additional information
?
-
-
vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes
-
-
?
additional information
?
-
-
vanin-1 regulates chondrogenesis via glutathione metabolism and is critical for accelerated chondrogenesis of ank/anf mesenchymal precursors and phosphate donor-driven chondrogenic transdifferentiation and calcification of aortic smooth muscle cells
-
-
?
additional information
?
-
-
vanin-1, by antagonizing PPARgamma, licenses the production of inflammatory mediators by intestinal epithelial cells
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,3-bis[(2-hydroxyethyl)thio]-1,4-naphthoquinone
-
i.e. NSC 95397, from library of pharmacologically active compounds, LOPAC
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
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
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
-
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
cystine
-
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
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
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
NEM
-
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
-
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
PCMB
-
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
additional information
-
no inhibition by 5 mM GSSG in absence or presence of substrate S-pantetheine-3-pyruvate
-
(R)-2,4-dihydroxy-3,3-dimethyl-N-(3-oxo-4-phenylbutyl)butanamide
i.e. RR6
(R)-2,4-dihydroxy-3,3-dimethyl-N-(3-oxo-4-phenylbutyl)butanamide
i.e. RR6, design, synthesis, and characterization of a novel pantetheine analogue, RR6, that acts as a selective, reversible, and competitive vanin inhibitor at nanomolar concentration. Oral administration of RR6 in rats completely inhibits plasma vanin activity and caused alterations of plasma lipid concentrations upon fasting
4,4'-dithiodipyridine
-
0.01 mM, 15 min, no residual activity in absence of substrate S-pantetheine-3-pyruvate, 13% residual activity in presence of the substrate S-pantetheine-3-pyruvate
iodoacetamide
-
0.1 mM, 15 min, 0.5% residual activity in absence of substrate S-pantetheine-3-pyruvate, 72% residual activity in presence of the substrate S-pantetheine-3-pyruvate
iodoacetate
-
1 mM, 15 min, 16% residual activity in absence of substrate S-pantetheine-3-pyruvate, 90% residual activity in presence of the substrate S-pantetheine-3-pyruvate
pantethine
-
0.01 mM, 15 min, no residual activity in absence of substrate S-pantetheine-3-pyruvate, 52% residual activity in presence of the substrate S-pantetheine-3-pyruvate
RR6
shows high specificity towards vanin 1 and competitively and reversibly inhibits pantetheinase activity at nanomolar concentration
RR6
-
shows high specificity towards vanin 1 and competitively and reversibly inhibits pantetheinase activity at nanomolar concentration
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
19fold upregultion of gene expression of vanin-1 psoriasis, vanin-1 expression in atopic dermatits little increased
-
additional information
19fold upregultion of gene expression of vanin-1 psoriasis, vanin-1 expression in atopic dermatits little increased
-
additional information
Q9NY84
19fold upregultion of gene expression of vanin-1 psoriasis, vanin-1 expression in atopic dermatits little increased
-
additional information
-
19fold upregultion of gene expression of vanin-1 psoriasis, vanin-1 expression in atopic dermatits little increased
-
additional information
induced expression of vanin-2 in psoriasis and atopic dermatitis
-
additional information
induced expression of vanin-2 in psoriasis and atopic dermatitis
-
additional information
Q9NY84
induced expression of vanin-2 in psoriasis and atopic dermatitis
-
additional information
-
induced expression of vanin-2 in psoriasis and atopic dermatitis
-
additional information
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-1 in reconstructed human epidermis
-
additional information
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-1 in reconstructed human epidermis
-
additional information
Q9NY84
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-1 in reconstructed human epidermis
-
additional information
-
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-1 in reconstructed human epidermis
-
additional information
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-3 in reconstructed human epidermis
-
additional information
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-3 in reconstructed human epidermis
-
additional information
Q9NY84
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-3 in reconstructed human epidermis
-
additional information
-
mixture of TNF-alpha, IL-1alpha and IL-6 results in increased expression of vanin-3 in reconstructed human epidermis
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Michaelis-Menten kinetics and Lineweaver-Burk plots
-
13
pantothenate-7-amido-4-methylcoumarin
-
apparent Km value, soluble recombinant vanin-1, pH 7.7, 25°C
28
pantothenate-7-amido-4-methylcoumarin
-
apparent Km value, HPLC assay, pH 7.7, 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0079
N2-(cis-2-aminocyclohexyl)-N6-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine hydrochloride
Homo sapiens
-
pH 7.5, 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
a simple, rapid, very sensitive, and specific continous spectrophotometric assay of pantetheinase activity
additional information
comparisons of healthy with Malaria red blood cells
additional information
comparisons of healthy with Malaria red blood cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
greatly reduced activity observed at both acidic (pH 3.0) and basic (pH 10.0) conditions
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
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
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Malaria diagnosed children living in Luanda (Angola) ranging from 6 months to 13 years of age
UniProt
-
-
-
mice injected i.p. with 106 Plasmodium berghei ANKA infected red blood cells
UniProt
mice injected i.p. with 106 Plasmodium berghei ANKA infected red blood cells
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
lung epithelial cells, transfected and selected for stable expression of human vanin-1
additional information
-
epithelium. Vanin-1 controls the inflammatory response in injured colon. Vanin-1 regulates the expression of PPARgamma in epithelial cells
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
-
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
-
regulation of VNN2 transcripts in bovine follicles prior to ovulation, high levels of gonadotropins regulate VNN2 mRNA expression in granulosa cells of bovine preovulatory follicles
-
regulation of VNN2 transcripts in bovine follicles prior to ovulation, high levels of gonadotropins regulate VNN2 mRNA expression in granulosa cells of bovine preovulatory follicles
-
vanin 1 expression specifically by the centrilobular hepatocytes in zone 3 adjacent to the central vein
vanin 1 expression specifically by the centrilobular hepatocytes in zone 3 adjacent to the central vein
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
-
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
-
-
higher level in kidney than in liver, similar expression in lung, determined by RT-PCR
ovulatory, regulation of VNN2 transcripts in bovine follicles prior to ovulation, high expression level during the ovulatory process
-
ovulatory, regulation of VNN2 transcripts in bovine follicles prior to ovulation, high expression level during the ovulatory process
-
normal skin, psoriatic lesions, atopic dermatitis lesions
-
the transcription factors steroidogenic factor-1 and SOX9 regulate expression of vanin-1 during mouse testis development
additional information
quantitative expression analysis of VNN-1 in cancer cells
additional information
-
quantitative expression analysis of VNN-1 in cancer cells
additional information
pantetheinase is a glycosylphosphatidylinositol (GPI) anchored enzyme, overexpressed in intestine, liver, and kidney
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
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
-
additional information
a glycosylphosphatidylinositol (GPI)-anchored ectoenzyme
pantetheinase is an ectoenzyme that is attached to the outer plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. GPI anchors consist of three domains: a phosphoethanolamine linker that attaches to the C terminal end of the target protein, a conserved glycan core and a phospholipid tail for anchoring to the lipid membrane
-
pantetheinase is an ectoenzyme that is attached to the outer plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. GPI anchors consist of three domains: a phosphoethanolamine linker that attaches to the C terminal end of the target protein, a conserved glycan core and a phospholipid tail for anchoring to the lipid membrane
-
-
the purified recombinant vanin-1 consists of a extracellular portion without a glycosylphosphatidylinositol linker
-
a glycosylphosphatidylinositol-anchored membrane pantetheinase
additional information
vanin 1 is membrane-associated via a glycosylphosphatidylinositol (GPI)-anchor, though soluble enzyme forms are detected as well
-
additional information
vanin 1 is membrane-associated via a glycosylphosphatidylinositol (GPI)-anchor, though soluble enzyme forms are detected as well
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
-
vanin 1 knockout mice display an enhanced resistance to oxidative stress and show down-regulated tissue inflammation in response to oxidative stress. Vanin knockout mice exhibit a loss of cysteamine-mediated inhibition of peroxisome proliferator-activated receptor gamma. Vanin 1 deficient islets are twice as susceptible to cell death as wild type cells
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
malfunction
evaluation of the effects of the inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc). The vanin-1/pantetheinase pathway is activated in wild-type BALB/c mice through hypochlorous acid (HOCl)-induced SSc. Hyperactivity of the vanin-1/pantetheinase pathway may reduce the vasculoprotective effects of pantethine, while genetic inactivation of vanin-1 has a protective effect
malfunction
mutant mice with a reduced serum pantetheinase activity are anemic and prone to phenylhydrazine-induced anemia. A cytofluorometric and spectroscopic analysis documents an increased frequency of erythrocytes with an autofluorescent aging phenotype. This is associated with an enhanced oxidative stress and shear stress-induced hemolysis. Red blood cell transfer and bone marrow chimera experiments show that the aging phenotype is not cell intrinsic but conferred by the environment, leading to a shortening of red blood cell half-life. Phenotype analysis, detailed overview
malfunction
PPAR-alpha KO mice show a negligible liver vnn1 expression, even after stimulation with various agonists. Vanin 1 overexpression increases glucose output by specifically increasing the hepatic transcription levels of gluconeogenic genes, while vnn1 knockdown decreases the glucose output of murine hepatocytes
malfunction
Vnn1 deficiency favors soft tissue sarcoma development in p16/p19-/- mice
malfunction
-
evaluation of the effects of the inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc). The vanin-1/pantetheinase pathway is activated in wild-type BALB/c mice through hypochlorous acid (HOCl)-induced SSc. Hyperactivity of the vanin-1/pantetheinase pathway may reduce the vasculoprotective effects of pantethine, while genetic inactivation of vanin-1 has a protective effect
-
malfunction
-
mutant mice with a reduced serum pantetheinase activity are anemic and prone to phenylhydrazine-induced anemia. A cytofluorometric and spectroscopic analysis documents an increased frequency of erythrocytes with an autofluorescent aging phenotype. This is associated with an enhanced oxidative stress and shear stress-induced hemolysis. Red blood cell transfer and bone marrow chimera experiments show that the aging phenotype is not cell intrinsic but conferred by the environment, leading to a shortening of red blood cell half-life. Phenotype analysis, detailed overview
-
metabolism
enzyme Vnn1 is a valid biomarker for aggressive soft tissue sarcomas (STS) prognosis. Analysis of a route to regulate tumor growth rates through the modulation of CoA and cysteamine levels
metabolism
-
formation of pantothenic acid allows for a continuous production of CoA, as pantothenic acid is a structural component of this cofactor. In addition, pantothenic acid appears to have profibrotic effects, being involved in the promotion of proliferation and migration of dermal fibroblasts. Moreover, pantothenic acid contributes to restoring CoA levels in the mitochondria, resulting in enhanced mitochondrial activity. Vanin 1 also plays a role in the regulation of a number of metabolic pathways
metabolism
formation of pantothenic acid allows for a continuous production of CoA, as pantothenic acid is a structural component of this cofactor. In addition, pantothenic acid appears to have profibrotic effects, being involved in the promotion of proliferation and migration of dermal fibroblasts. Moreover, pantothenic acid contributes to restoring CoA levels in the mitochondria, resulting in enhanced mitochondrial activity. Vanin 1 also plays a role in the regulation of a number of metabolic pathways
metabolism
formation of pantothenic acid allows for a continuous production of CoA, as pantothenic acid is a structural component of this cofactor. In addition, pantothenic acid appears to have profibrotic effects, being involved in the promotion of proliferation and migration of dermal fibroblasts. Moreover, pantothenic acid contributes to restoring CoA levels in the mitochondria, resulting in enhanced mitochondrial activity. Vanin 1 also plays a role in the regulation of a number of metabolic pathways
metabolism
formation of pantothenic acid allows for a continuous production of CoA, as pantothenic acid is a structural component of this cofactor. In addition, pantothenic acid appears to have profibrotic effects, being involved in the promotion of proliferation and migration of dermal fibroblasts. Moreover, pantothenic acid contributes to restoring CoA levels in the mitochondria, resulting in enhanced mitochondrial activity. Vanin 1 also plays a role in the regulation of a number of metabolic pathways. In fact, the vnn1 gene is one of the positive targets of the peroxisome proliferator-activated receptor alpha (PPAR-alpha) in mouse liver. PPAR-alpha is a key regulator of the liver's response to fasting
metabolism
inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc)
metabolism
the availability of free cysteamine is also regulated by hydrolysis of pantetheine by pantetheinase. This cleavage results in the formation of pantothenic acid, a precursor to coenzyme A which is prominently involved with lipid metabolism and energy production by the beta-oxidation pathway and TCA cycle, respectively. Expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. Vanin-1 is believed to be the primary transcript responsible for pantetheinase activity. Successful attachment of GPI following its synthesis in the endoplasmic reticulum (ER) requires two signal sequences within the protein. The first is an N terminal signal peptide (amino acids 1-21 of human pantetheinase) that retains the target protein within the ER lumen. The second necessary sequence is a C-terminal 22 amino acid propeptide downstream of the Gly491 residue, termed the omega site, which is removed and replaced by the GPI anchor. This process is mediated by a GPI-transamidase complex composed mainly of members of the phosphatidylinositol glycan (PIG) family, including PIG-K, the catalytic subunit
metabolism
-
inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc)
-
metabolism
-
the availability of free cysteamine is also regulated by hydrolysis of pantetheine by pantetheinase. This cleavage results in the formation of pantothenic acid, a precursor to coenzyme A which is prominently involved with lipid metabolism and energy production by the beta-oxidation pathway and TCA cycle, respectively. Expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. Vanin-1 is believed to be the primary transcript responsible for pantetheinase activity. Successful attachment of GPI following its synthesis in the endoplasmic reticulum (ER) requires two signal sequences within the protein. The first is an N terminal signal peptide (amino acids 1-21 of human pantetheinase) that retains the target protein within the ER lumen. The second necessary sequence is a C-terminal 22 amino acid propeptide downstream of the Gly491 residue, termed the omega site, which is removed and replaced by the GPI anchor. This process is mediated by a GPI-transamidase complex composed mainly of members of the phosphatidylinositol glycan (PIG) family, including PIG-K, the catalytic subunit
-
physiological function
-
overexpression of vanin-1 is most strongly associated with progression to chronic pediatric immune thrombocytopenia. Vanin-1 is a peripheral blood oxidative stress sensor
physiological function
-
vanin plays a role in inflammation, oxidative stress, cell migration and numerous diseases including cardiovascular disease (increased vanin 1 activity has a protective effect against cardiovascular disease). Vanin 1 has a cytoprotective effect against type 1 diabetes in islet cells. Vanin 1 is a central regulator of not only stress responses via production of cysteamine but also lipid biosynthesis by controlling the flux through the fatty acid and/or cholesterol biosynthetic pathways
physiological function
-
vanin plays a role in inflammation, oxidative stress, cell migration and numerous diseases including cardiovascular disease (increased vanin 1 activity has a protective effect against cardiovascular disease). Vanin 1 has a cytoprotective effect against type 1 diabetes in islet cells. Vanin 1 is a central regulator of not only stress responses via production of cysteamine but also lipid biosynthesis by controlling the flux through the fatty acid and/or cholesterol biosynthetic pathways
physiological function
vanin-2 is known to be involved in inflammation and leukocyte migration
physiological function
vanins are enzymes with pantetheinase activity and are presumed to play a role in the recycling of pantothenic acid (vitamin B5) from pantetheine. Pantothenic acid is an essential nutrient required to synthesize coenzyme A, a cofactor involved in many biological processes such as fatty acid synthesis and oxidation of pyruvate to fuel the citric acid cycle. Hydrolysis of pantetheine also liberates cysteamine, a known antioxidant
physiological function
pantetheinase hydrolyzes pantetheine to pantothenic acid (Vitamin B5) in a reaction that cleaves cysteamine from the pantetheine molecule. Pantetheinase activity regulates the availability of pantothenic acid and cysteamine which are involved in several critical pathways of cell homeostasis including lipid catabolism, synthesis of cholesterol, taurine and NADH as well as maintenance of cellular redox balance. Vascular non-inflammatory molecule 1 (Vanin 1 or Vnn1) modulates redox and immune pathways in vivo, both of which appear at least partially due to a loss of cysteamine/cystamine. Vnn1 expression may influence cell signaling indirectly through maintenance of disulfide bonds or directly by interaction with pantetheinase on the cell surface. Involvement of vanin-1 and pantetheinase in liver homeostasis. Pantetheinase activity can directly influence lipid metabolism, the effects are due to decreased availability of pantothenic acid, resulting in suppression of CoA activity. Pantetheinase likely acts as a regulator of CoA-dependent metabolism by controlling the availability of pantothenic acid in liver. Pantetheinase-mediated catalysis is the main source of endogenous cysteamine in mice. Pantetheinase activity might be protective by augmenting the availability of taurine
physiological function
pantetheinase is a glycosylphosphatidylinositol (GPI) anchored enzyme, overexpressed in intestine, liver, and kidney with various biological functions such as its linkage to the inflammation and some metabolic diseases. It can hydrolyze pantetheine to cysteamine, an antioxidant, and pantothenic acid (vitamin B5) that is an essential component of coenzyme A (CoA). Starvation induces pantetheinase upregulation
physiological function
the vanin-1 (vascular noninflammatory molecule 1, VNN1) gene encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Pantetheine significantly reduces the IAV replication and influenza A virus (IAV) matrix 1 (M1) mRNA levels when it is administered prior to and during infection. Cysteamine treatment during IAV infection significantly reduces the viral replication and IAV M1 mRNA levels, whereas pantothenic acid does not. The metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia
physiological function
the vanin-1 gene (vnn1) encodes an enzyme with pantetheinase activity that converts vasculoprotective pantethine into profibrotic pantothenic acid and pro-oxidant cystamine. By hydrolyzation of pantethine, vanin-1 delivers cysteamine and pantothenic acid to tissues. Cysteamine is rapidly converted into cystamine that can regulate the function of other target proteins by a disulfide reaction. In particular, cystamine abrogates glutathione (GSH) production by inhibiting gamma-glutamyl synthase, the rate-limiting enzyme of GSH synthesis, thus strongly reducing reactive oxygen species (ROS) scavenging. In contrast, pantothenic acid, the other by-product of vanin-1, exerts profibrotic effects by promoting the proliferation and migration of dermal fibroblasts, as well as collagen synthesis
physiological function
tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress. VNN genes contribute to the susceptibility to malaria. Serum pantetheinase contributes to erythrocyte resistance to stress under homeostatic conditions. Serum pantetheinase level regulates erythrocyte life span and modulates the risk of developing complicated malaria
physiological function
tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress. VNN genes contribute to the susceptibility to malaria. Serum pantetheinase contributes to erythrocyte resistance to stress under homeostatic conditions. Serum pantetheinase level regulates erythrocyte life span and modulates the risk of developing complicated malaria
physiological function
-
vanin 1 breaks down pantetheine in cysteamine and pantothenic acid, a precursor of coenzyme A. Its physiological role is not strictly related to coenzyme A metabolism, lipid metabolism, and energy production. It also plays a role under physiological conditions in relation to oxidative stress and inflammation. Vanin's enzymatic activity is of key importance in certain diseases, either for its protective effect or as a sensitizer, depending on the diseased organ. But vanin-1's primary function is the recycling of pantothenic acid (vitamin B5), an important precursor in the biosynthesis of coenzymeA (CoA). Vanin 1 also plays a role in the regulation of a number of metabolic pathways
physiological function
vanin 1 breaks down pantetheine in cysteamine and pantothenic acid, a precursor of coenzyme A. Its physiological role is not strictly related to coenzyme A metabolism, lipid metabolism, and energy production. It also plays a role under physiological conditions in relation to oxidative stress and inflammation. Vanin's enzymatic activity is of key importance in certain diseases, either for its protective effect or as a sensitizer, depending on the diseased organ. But vanin-1's primary function is the recycling of pantothenic acid (vitamin B5), an important precursor in the biosynthesis of coenzymeA (CoA). Vanin 1 also plays a role in the regulation of a number of metabolic pathways
physiological function
vanin 1 breaks down pantetheine in cysteamine and pantothenic acid, a precursor of coenzyme A. Its physiological role is not strictly related to coenzyme A metabolism, lipid metabolism, and energy production. It also plays a role under physiological conditions in relation to oxidative stress and inflammation. Vanin's enzymatic activity is of key importance in certain diseases, either for its protective effect or as a sensitizer, depending on the diseased organ. But vanin-1's primary function is the recycling of pantothenic acid (vitamin B5), an important precursor in the biosynthesis of coenzymeA (CoA). Vanin 1 also plays a role in the regulation of a number of metabolic pathways. Gene vnn1 directly regulates PPAR-alpha mRNA expression in gut epithelial. Vanin 1 is an activator of hepatic gluconeogenesis in mice. Role of vanin 1 in diseases of organs in which it is highly expressed (liver, kidney, intestine, lung), detailed overview
physiological function
vanin 1 breaks down pantetheine in cysteamine and pantothenic acid, a precursor of coenzyme A. Its physiological role is not strictly related to coenzyme A metabolism, lipid metabolism, and energy production. It also plays a role under physiological conditions in relation to oxidative stress and inflammation. Vanin's enzymatic activity is of key importance in certain diseases, either for its protective effect or as a sensitizer, depending on the diseased organ. But vanin-1's primary function is the recycling of pantothenic acid (vitamin B5), an important precursor in the biosynthesis of coenzymeA (CoA). Vanin 1 also plays a role in the regulation of a number of metabolic pathways. Role of vanin 1 in diseases of organs in which it is highly expressed (liver, kidney, intestine, lung), detailed overview
physiological function
Vnn1 pantetheinase acts as a tumor suppressor for the development of aggressive soft tissue sarcomas (STS). The two products of pantetheinase activity exert complementary effects on the tumor, explaining the basis for Vnn1's suppression on tumor growth. Pantothenate production restores CoA levels leading to an enhanced mitochondrial activity, whereas cysteamine reduces glycolysis and prevents the transition to the Warburg effect, a feature of the most aggressive tumors. Vnn1 expression antagonizes the glycolytic switch in Ras-driven tumors. Vnn1 expression antagonizes the glycolytic switch in Ras-driven tumors
physiological function
-
the vanin-1 gene (vnn1) encodes an enzyme with pantetheinase activity that converts vasculoprotective pantethine into profibrotic pantothenic acid and pro-oxidant cystamine. By hydrolyzation of pantethine, vanin-1 delivers cysteamine and pantothenic acid to tissues. Cysteamine is rapidly converted into cystamine that can regulate the function of other target proteins by a disulfide reaction. In particular, cystamine abrogates glutathione (GSH) production by inhibiting gamma-glutamyl synthase, the rate-limiting enzyme of GSH synthesis, thus strongly reducing reactive oxygen species (ROS) scavenging. In contrast, pantothenic acid, the other by-product of vanin-1, exerts profibrotic effects by promoting the proliferation and migration of dermal fibroblasts, as well as collagen synthesis
-
physiological function
-
pantetheinase hydrolyzes pantetheine to pantothenic acid (Vitamin B5) in a reaction that cleaves cysteamine from the pantetheine molecule. Pantetheinase activity regulates the availability of pantothenic acid and cysteamine which are involved in several critical pathways of cell homeostasis including lipid catabolism, synthesis of cholesterol, taurine and NADH as well as maintenance of cellular redox balance. Vascular non-inflammatory molecule 1 (Vanin 1 or Vnn1) modulates redox and immune pathways in vivo, both of which appear at least partially due to a loss of cysteamine/cystamine. Vnn1 expression may influence cell signaling indirectly through maintenance of disulfide bonds or directly by interaction with pantetheinase on the cell surface. Involvement of vanin-1 and pantetheinase in liver homeostasis. Pantetheinase activity can directly influence lipid metabolism, the effects are due to decreased availability of pantothenic acid, resulting in suppression of CoA activity. Pantetheinase likely acts as a regulator of CoA-dependent metabolism by controlling the availability of pantothenic acid in liver. Pantetheinase-mediated catalysis is the main source of endogenous cysteamine in mice. Pantetheinase activity might be protective by augmenting the availability of taurine
-
physiological function
-
tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress. VNN genes contribute to the susceptibility to malaria. Serum pantetheinase contributes to erythrocyte resistance to stress under homeostatic conditions. Serum pantetheinase level regulates erythrocyte life span and modulates the risk of developing complicated malaria
-
physiological function
-
vanin-2 is known to be involved in inflammation and leukocyte migration
-
additional information
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
additional information
-
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
additional information
-
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
-
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). VNN1_BOVIN
510
0
56947
Swiss-Prot
Secretory Pathway (Reliability: 1)
VNN1_CANLF
514
0
57432
Swiss-Prot
Secretory Pathway (Reliability: 1)
VNN1_HUMAN
513
0
57012
Swiss-Prot
Secretory Pathway (Reliability: 1)
VNN1_MOUSE
512
0
57091
Swiss-Prot
Secretory Pathway (Reliability: 1)
VNN1_PIG
513
1
57156
Swiss-Prot
Secretory Pathway (Reliability: 1)
VNN2_HUMAN
520
1
58503
Swiss-Prot
Secretory Pathway (Reliability: 1)
A0A6J8AA59_MYTCO
444
0
50181
TrEMBL
other Location (Reliability: 2)
A0A812DBZ4_SEPPH
580
3
66215
TrEMBL
Secretory Pathway (Reliability: 1)
A0A6J8BW13_MYTCO
478
0
54562
TrEMBL
other Location (Reliability: 3)
A0A7R8CW08_LEPSM
417
0
47038
TrEMBL
Secretory Pathway (Reliability: 1)
A0A8B6FZI2_MYTGA
399
0
46246
TrEMBL
Secretory Pathway (Reliability: 4)
A0A061ICY3_CRIGR
512
1
56765
TrEMBL
Secretory Pathway (Reliability: 1)
B7PHC3_IXOSC
466
0
52560
TrEMBL
Secretory Pathway (Reliability: 1)
A0A812D8R5_SEPPH
492
0
55813
TrEMBL
Secretory Pathway (Reliability: 1)
G3I739_CRIGR
377
1
42350
TrEMBL
Secretory Pathway (Reliability: 1)
Q5M8L7_XENTR
501
0
56140
TrEMBL
Secretory Pathway (Reliability: 2)
A0A8B6F881_MYTGA
455
0
51338
TrEMBL
other Location (Reliability: 1)
A0A6J8ANP5_MYTCO
524
0
58877
TrEMBL
Secretory Pathway (Reliability: 1)
A0A8B6FZ88_MYTGA
495
0
57402
TrEMBL
other Location (Reliability: 2)
A0A8B6HN31_MYTGA
509
0
57468
TrEMBL
Secretory Pathway (Reliability: 2)
A0A6J8D8E2_MYTCO
507
0
56907
TrEMBL
Secretory Pathway (Reliability: 1)
A0A6J8BSA9_MYTCO
327
0
37403
TrEMBL
other Location (Reliability: 4)
A0A6J8A8E9_MYTCO
443
0
50480
TrEMBL
other Location (Reliability: 5)
A0A2G9HDR2_9LAMI
172
0
20239
TrEMBL
Mitochondrion (Reliability: 5)
A0A8B6E9N6_MYTGA
538
2
60359
TrEMBL
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
54000
58000
60000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oligomer
the residues important for oligomerization are Gln179-Phe182, Pro191-Glu193, Phe212-Asp218, Pro243-His251 and Leu326-Asn330
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycolipoprotein
glycoprotein
lipoprotein
a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase
glycolipoprotein
a glycosylphosphatidylinositol (GPI)-anchored ectoenzyme
glycolipoprotein
a glycosylphosphatidylinositol-anchored pantetheinase
glycoprotein
-
presence of galactose, mannose, fucose, glucose, galactosamine and sialic acid, 11.8% total carbohydrate content
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
T26I
additional information
T26I
naturally occuring mutation, similar vanin-1 protein levels are detected in cells expressing T26I vanin-1 compared to cells expressing wild-type vanin-1
additional information
construction of several VNN2 promoter-deletion mutants: deletion of the region between -1107 and -530 result in a marked and significant increase of basal and forskolin-stimulated promoter activities, suggesting factors repressing the promoter activity in this region. This region contains a number of consensus cis-acting elements of which COUP-TF, GATA, and Ebox appears to play a key role, as revealed by site-directed mutagenesis and promoter activity assays. Deletion between -530 and -262 markedly decreased basal and forskolin-stimulated promoter activities as compared to the-530VNN2.LUC construct. Further deletions do not change promoter activities, thus identifying the region -530/-262 as important in the regulation of the VNN2 promoter activity in bovine granulosa cells
additional information
-
construction of several VNN2 promoter-deletion mutants: deletion of the region between -1107 and -530 result in a marked and significant increase of basal and forskolin-stimulated promoter activities, suggesting factors repressing the promoter activity in this region. This region contains a number of consensus cis-acting elements of which COUP-TF, GATA, and Ebox appears to play a key role, as revealed by site-directed mutagenesis and promoter activity assays. Deletion between -530 and -262 markedly decreased basal and forskolin-stimulated promoter activities as compared to the-530VNN2.LUC construct. Further deletions do not change promoter activities, thus identifying the region -530/-262 as important in the regulation of the VNN2 promoter activity in bovine granulosa cells
additional information
-
construction of several VNN2 promoter-deletion mutants: deletion of the region between -1107 and -530 result in a marked and significant increase of basal and forskolin-stimulated promoter activities, suggesting factors repressing the promoter activity in this region. This region contains a number of consensus cis-acting elements of which COUP-TF, GATA, and Ebox appears to play a key role, as revealed by site-directed mutagenesis and promoter activity assays. Deletion between -530 and -262 markedly decreased basal and forskolin-stimulated promoter activities as compared to the-530VNN2.LUC construct. Further deletions do not change promoter activities, thus identifying the region -530/-262 as important in the regulation of the VNN2 promoter activity in bovine granulosa cells
-
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
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
additional information
construction of in p16/p19-/- mutant mice. Comparison of mouse survival and tumor incidence in three independent cohorts of p16/p19/Vnn1-/- versus p16/p19-/- mice, derived from two independently derived crosses between p16/p19-/- and Vnn1-/- mice. Whereas 35% p16p19-/- mice progressively develop lethal tumors within 220 days, 70% p16p19/Vnn1-/- die of aggressive tumors before 220 days. Whereas p16p19-/- mice develop various tumor types with a majority of lymphomas, p16/p19/Vnn1-/- mice predominantly develop skin STS typed as fibrosarcomas
additional information
development of vnn1 KO mice, which do not have an obvious spontaneous phenotype, they are resistant to inflammation and oxidative stress, thus indisputably proving a correlation between vanin 1, its pantetheinase activity and pro-inflammatory mediators
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
gene Vnn1, quantitative RT-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
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
expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. PPARalpha-mediated upregulation of Vnn1 translates to enhanced pantetheinase activity in vivo
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
-
inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc)
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
PPAR-alpha KO mice show a negligible liver vnn1 expression, even after stimulation with various agonists
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 messenger RNA expression of VNN1 in A549 cells is significantly increased (by 4.9fold) after influenza A virus (IAV) infection under an elevated concentration of pantetheine. VNN1 mRNA levels are elevated by over 100fold in response to proinflammatory cytokines, especially TNF-alpha and IL-1beta
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
-
upon administration of the PPAR-alpha agonists fenofibrate, clofibrate, or Wy-14,643, gene vnn1 expression is increased. The transcription of vnn1 itself is activated by PPAR-alpha coactivator 1 (PGC-1) in complex with the hepatocyte nuclear factor-4alpha (HNF-4alpha). In turn, this complex is mediated by the Akt signaling pathway
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
expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. PPARalpha-mediated upregulation of Vnn1 translates to enhanced pantetheinase activity in vivo
expression of pantetheinase is controlled by the Vnn1 gene and is upregulated in response to free fatty acids, PPAR activation or oxidative stress. PPARalpha-mediated upregulation of Vnn1 translates to enhanced pantetheinase activity in vivo
-
-
inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc)
inactivation of vnn1 on the development of fibrosis, endothelial alterations, and immunological activation in mice with HOCl- and bleomycin-induced systemic sclerosis (SSc)
-
-
mRNA expressions of vanin-1 significantly increases in the kidney, but not in the colon, during colitis
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
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
-
-
VNN2 promoter activity and mRNA expression are inhibited by protein kinase A and ERK1/2 inhibitors
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
VNN2 promoter activity and mRNA expression are markedly stimulated by forskolin and overexpression of the catalytic subunit of protein kinase A
-
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
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
diagnostics
usefulness of urinary vanin-1 with other biomarkers for the detection of renal complications in rats with experimental colitis
diagnostics
vanin-1 is a biomarker of nephrotoxicant-induced kidney injury, increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-beta-glucosaminidase, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin, in models of drug-induced acute kidney injury, overview
diagnostics
enzyme Vnn1 is a valid biomarker for aggressive soft tissue sarcomas (STS) prognosis
diagnostics
potential use of vanin-1 as a marker of severity and therapeutic target in systemic sclerosis (SSc)
diagnostics
-
potential use of vanin-1 as a marker of severity and therapeutic target in systemic sclerosis (SSc)
-
diagnostics
-
usefulness of urinary vanin-1 with other biomarkers for the detection of renal complications in rats with experimental colitis
-
diagnostics
-
vanin-1 is a biomarker of nephrotoxicant-induced kidney injury, increase in urinary vanin-1 is detected before the elevations of serum creatinine or urinary N-acetyl-beta-glucosaminidase, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin, in models of drug-induced acute kidney injury, overview
-
medicine
-
the pantetheinase activity of vanin-1 molecule could be a target for a new anti-inflammatory strategy
medicine
-
manipulation the Vanin-1/pantetheinase activity represents an attractive therapeutic strategy for the treatment of inflammatory bowel disease
medicine
-
vanin-1 is a potential biomarker for nephrotoxicant-induced renal injury
medicine
-
vanin-1 is a potential biomarker for nephrotoxicant-induced renal injury
REF.
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TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Dupre, S.; Chiaraluce, R.; Nardini, M.; Cannella, C.; Ricci, G.; Cavallini, D.
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1984
Equus caballus
Ricci, G.; Nardini, M.; Chiaraluce, R.; Dupre, S.; Cavallini, D.
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Biochim. Biophys. Acta
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1986
Sus scrofa
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Eur. J. Biochem.
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Is pantetheinase the actual identity of mouse and human vanin-1 proteins?
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461
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Mus musculus, Sus scrofa
Pitari, G.; Malergue, F.; Martin, F.; Philippe, J.M.; Massucci, M.T.; Chabret, C.; Maras, B.; Dupre, S.; Naquet, P.; Galland, F.
Pantetheinase activity of membrane-bound vanin-1: lack of free cysteamine in tissues of vanin-1 deficient mice
FEBS Lett.
483
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2000
Mus musculus
Bowles, J.; Bullejos, M.; Koopman, P.
A subtractive gene expression screen suggests a role for vanin-1 in testis development in mice
Genesis
27
124-135
2000
Mus musculus
Aurrand-Lions, M.; Galland, F.; Bazin, H.; Zakharyev, V.M.; Imhof, B.A.; Naquet, P.
Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing
Immunity
5
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1996
Mus musculus
Martin, F.; Malergue, F.; Pitari, G.; Philippe, J.M.; Philips, S.; Chabret, C.; Granjeaud, S.; Mattei, M.G.; Mungall, A.J.; Naquet, P.; Galland, F.
Vanin genes are clustered (human 6q22-24 and mouse 10A2B1) and encode isoforms of pantetheinase ectoenzymes
Immunogenetics
53
296-306
2001
Mus musculus
Wittwer, C.T.; Burkhard, D.; Ririe, K.; Rasmussen, R.; Brown, J.; Wyse, B.W.; Hansen, R.G.
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Wilson, M.J.; Jeyasuria, P.; Parker, K.L.; Koopman, P.
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280
5917-5923
2005
Mus musculus
Martin, F.; Penet, M.F.; Malergue, F.; Lepidi, H.; Dessein, A.; Galland, F.; de Reggi, M.; Naquet, P.; Gharib, B.
Vanin-1(-/-) mice show decreased NSAID- and Schistosoma-induced intestinal inflammation associated with higher glutathione stores
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113
591-597
2004
Mus musculus
Calvino, J.A.; Barcia, R.
Purification and properties of pantetheinase from pig kidney
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26
103-118
2002
Sus scrofa
Wittwer, C.T.; Wyse, B.W.; Hansen, R.G.
Enzymic hydrolysis of pantetheine
Methods Enzymol.
122
36-43
1986
Sus scrofa
Dupre, S.; Cavallini, D.
Purification and properties of pantetheinase from horse kidney
Methods Enzymol.
62
262-267
1979
Equus caballus
Berruyer, C.; Martin, F.M.; Castellano, R.; Macone, A.; Malergue, F.; Garrido-Urbani, S.; Millet, V.; Imbert, J.; Dupre, S.; Pitari, G.; Naquet, P.; Galland, F.
Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress
Mol. Cell. Biol.
24
7214-7224
2004
Mus musculus
Johnson, K.A.; Yao, W.; Lane, N.E.; Naquet, P.; Terkeltaub, R.A.
Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice
Am. J. Pathol.
172
440-453
2008
Mus musculus
Roisin-Bouffay, C.; Castellano, R.; Valero, R.; Chasson, L.; Galland, F.; Naquet, P.
Mouse vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes
Diabetologia
51
1192-1201
2008
Mus musculus
Meghari, S.; Berruyer, C.; Lepidi, H.; Galland, F.; Naquet, P.; Mege, J.L.
Vanin-1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection
Eur. J. Immunol.
37
24-32
2007
Mus musculus
Berruyer, C.; Pouyet, L.; Millet, V.; Martin, F.M.; LeGoffic, A.; Canonici, A.; Garcia, S.; Bagnis, C.; Naquet, P.; Galland, F.
Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor gamma activity
J. Exp. Med.
203
2817-2827
2006
Mus musculus
Nitto, T.; Inoue, T.; Node, K.
Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils
Gene
426
57-64
2008
Homo sapiens (O95497), Homo sapiens (O95498), Homo sapiens (Q9NY84), Homo sapiens
Jansen, P.A.; Kamsteeg, M.; Rodijk-Olthuis, D.; van Vlijmen-Willems, I.M.; de Jongh, G.J.; Bergers, M.; Tjabringa, G.S.; Zeeuwen, P.L.; Schalkwijk, J.
Expression of the Vanin Gene Family in Normal and Inflamed Human Skin: Induction by Proinflammatory Cytokines
J. Invest. Dermatol.
129
2167-2174
2009
Homo sapiens (O95497), Homo sapiens (O95498), Homo sapiens (Q9NY84), Homo sapiens
Ruan, B.H.; Cole, D.C.; Wu, P.; Quazi, A.; Page, K.; Wright, J.F.; Huang, N.; Stock, J.R.; Nocka, K.; Aulabaugh, A.; Krykbaev, R.; Fitz, L.J.; Wolfman, N.M.; Fleming, M.L.
A fluorescent assay suitable for inhibitor screening and vanin tissue quantification
Anal. Biochem.
399
284-292
2010
Homo sapiens, Mus musculus
Kaskow, B.J.; Michael Proffit, J.; Blangero, J.; Moses, E.K.; Abraham, L.J.
Diverse biological activities of the vascular non-inflammatory molecules - the Vanin pantetheinases
Biochem. Biophys. Res. Commun.
417
653-658
2012
Homo sapiens, Mus musculus
Zhang, B.; Lo, C.; Shen, L.; Sood, R.; Jones, C.; Cusmano-Ozog, K.; Park-Snyder, S.; Wong, W.; Jeng, M.; Cowan, T.; Engleman, E.G.; Zehnder, J.L.
The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP
Blood
117
4569-4579
2011
Homo sapiens
Hosohata, K.; Ando, H.; Fujiwara, Y.; Fujimura, A.
Vanin-1: a potential biomarker for nephrotoxicant-induced renal injury
Toxicology
290
82-88
2011
Homo sapiens, Rattus norvegicus
Jansen, P.A.; van Diepen, J.A.; Ritzen, B.; Zeeuwen, P.L.; Cacciatore, I.; Cornacchia, C.; van Vlijmen-Willems, I.M.; de Heuvel, E.; Botman, P.N.; Blaauw, R.H.; Hermkens, P.H.; Rutjes, F.P.; Schalkwijk, J.
Discovery of small molecule vanin inhibitors: new tools to study metabolism and disease
ACS Chem. Biol.
8
530-534
2013
Rattus norvegicus (Q4KLZ0)
Boersma, Y.L.; Newman, J.; Adams, T.E.; Cowieson, N.; Krippner, G.; Bozaoglu, K.; Peat, T.S.
The structure of vanin 1: a key enzyme linking metabolic disease and inflammation
Acta Crystallogr. Sect. D
70
3320-3329
2014
Homo sapiens (O95497), Homo sapiens
Sayasith, K.; Sirois, J.; Lussier, J.G.
Expression, regulation, and promoter activation of vanin-2 (VNN2) in bovine follicles prior to ovulation
Biol. Reprod.
89
98
2013
Bos taurus (A5D9D1), Bos taurus, Bos taurus Holstein (A5D9D1)
Hosohata, K.; Ando, H.; Fujimura, A.
Early detection of renal injury using urinary vanin-1 in rats with experimental colitis
J. Appl. Toxicol.
34
184-190
2014
Rattus norvegicus (Q4KLZ0), Rattus norvegicus, Rattus norvegicus Wistar (Q4KLZ0)
Hosohata, K.; Ando, H.; Fujimura, A.
Urinary vanin-1 as a novel biomarker for early detection of drug-induced acute kidney injury
J. Pharmacol. Exp. Ther.
341
656-662
2012
Rattus norvegicus (Q4KLZ0), Rattus norvegicus Wistar (Q4KLZ0)
Wang, Y.J.; Tayo, B.O.; Bandyopadhyay, A.; Wang, H.; Feng, T.; Franceschini, N.; Tang, H.; Gao, J.; Sung, Y.J.; Sung, Y.J.; Elston, R.C.; Williams, S.M.; Cooper, R.S.; Mu, T.W.; Zhu, X.
The association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function
PLoS Genet.
10
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2014
Homo sapiens (O95497)
Rommelaere, S.; Millet, V.; Rihet, P.; Atwell, S.; Helfer, E.; Chasson, L.; Beaumont, C.; Chimini, G.; Sambo, M.d.o. .R.; Viallat, A.; Penha-Goncalves, C.; Galland, F.; Naquet, P.
Serum pantetheinase/vanin levels regulate erythrocyte homeostasis and severity of malaria
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185
3039-3052
2015
Homo sapiens (O95497), Homo sapiens, Mus musculus (Q9Z0K8), Mus musculus, Mus musculus C57BL/6 (Q9Z0K8)
Lin, Y.; Gao, Y.; Ma, Z.; Li, Z.; Tang, C.; Qin, X.; Zhang, Z.; Wang, G.; Du, L.; Li, M.
Bioluminescent probe for detection of starvation-induced pantetheinase upregulation
Anal. Chem.
90
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2018
Mus musculus (Q9Z0K8)
Yamashita, N.; Yashiro, M.; Ogawa, H.; Namba, H.; Nosaka, N.; Fujii, Y.; Morishima, T.; Tsukahara, H.; Yamada, M.
Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells
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489
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2017
Homo sapiens (O95497), Homo sapiens
Ferreira, D.W.; Naquet, P.; Manautou, J.E.
Influence of vanin-1 and catalytic products in liver during normal and oxidative stress conditions
Curr. Med. Chem.
22
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2015
Mus musculus (Q9Z0K8), Mus musculus C57BL/6 (Q9Z0K8)
Bartucci, R.; Salvati, A.; Olinga, P.; Boersma, Y.L.
Vanin 1 its physiological function and role in diseases
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20
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Homo sapiens (O95497)
Bartucci, R.; Salvati, A.; Olinga, P.; Boersma, Y.L.
Vanin 1 its physiological function and role in diseases
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20
E3891
2019
Rattus norvegicus, Sus scrofa (Q9BDJ5), Mus musculus (Q9Z0K8)
Kavian, N.; Mehlal, S.; Marut, W.; Servettaz, A.; Giessner, C.; Bourges, C.; Nicco, C.; Chereau, C.; Lemarechal, H.; Dutilh, M.F.; Cerles, O.; Guilpain, P.; Vuiblet, V.; Chouzenoux, S.; Galland, F.; Quere, I.; Weill, B.; Naquet, P.; Batteux, F.
Imbalance of the vanin-1 pathway in systemic sclerosis
J. Immunol.
197
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2016
Mus musculus (Q9Z0K8), Mus musculus BALB/c (Q9Z0K8)
Giessner, C.; Millet, V.; Mostert, K.J.; Gensollen, T.; Vu Manh, T.P.; Garibal, M.; Dieme, B.; Attaf-Bouabdallah, N.; Chasson, L.; Brouilly, N.; Laprie, C.; Lesluyes, T.; Blay, J.Y.; Shintu, L.; Martin, J.C.; Strauss, E.; Galland, F.; Naquet, P.
Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity
Life Sci. Alliance
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Mus musculus (Q9Z0K8)
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