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

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IUBMB 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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Homo sapiens
UNIPROT: O95498
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
vanin-1, pantetheinase, gpi-80, vanin, pagel, vanin 1, pantetheinases, vanin-3, vanin-2, vascular noninflammatory molecule 1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pantetheinase
-
pantetheinases
-
vanin gene family
-
PAGEL
Q9NY84
-
pantetheinase
pantetheinase-associated gene expressed in leukocytes
Q9NY84
-
pantetheinases
O95497, Q9NY84
-
vanin 1
vanin gene family
O95497, Q9NY84
-
vanin-1
vanin-1 pantetheinase
-
vanin-3
Q9NY84
-
vascular non-inflammatory molecule-1
-
vascular noninflammatory molecule 1
-
VNN-1
-
-
VNN3
Q9NY84
-
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 hide
56093-18-6
-
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 SUBSTRATE
NATURAL 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
-
-
-
-
?
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
INHIBITOR
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
-
cytokine Th1
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8
-
-
7.5
-
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
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
O95497, O95498, Q9NY84
normal skin, psoriatic lesions, atopic dermatitis lesions
Manually annotated by BRENDA team
vanin 1 expression specifically by the centrilobular hepatocytes in zone 3 adjacent to the central vein
Manually annotated by BRENDA team
-
peripheral blood leukocyte
Manually annotated by BRENDA team
-
lung epithelial cells, transfected and selected for stable expression of human vanin-1
Manually annotated by BRENDA team
O95497, O95498, Q9NY84
normal skin, psoriatic lesions, atopic dermatitis lesions
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
O95497, O95498, Q9NY84
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
-
Manually annotated by BRENDA team
additional information
vanin 1 is membrane-associated via a glycosylphosphatidylinositol (GPI)-anchor, though soluble enzyme forms are detected as well
-
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
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
VNN2_HUMAN
520
1
58503
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54000
-
size exclusion chromatography-multiangular light scattering (SEC-MALS)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
PROTEIN VARIANTS
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
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 VNN-1, quantitative real-time RT-PCR expression analysis
gene Vnn1, quantitative RT-PCR enzyme expression analysis
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
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 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
-
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
e1004641
2014
Homo sapiens (O95497)
Manually annotated by BRENDA team
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
Am. J. Pathol.
185
3039-3052
2015
Homo sapiens (O95497), Homo sapiens, Mus musculus (Q9Z0K8), Mus musculus, Mus musculus C57BL/6 (Q9Z0K8)
Manually annotated by BRENDA team
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
Biochem. Biophys. Res. Commun.
489
466-471
2017
Homo sapiens (O95497), Homo sapiens
Manually annotated by BRENDA team
Bartucci, R.; Salvati, A.; Olinga, P.; Boersma, Y.L.
Vanin 1 its physiological function and role in diseases
Int. J. Mol. Sci.
20
3891
2019
Homo sapiens (O95497)
Manually annotated by BRENDA team