vanin 1 | Hydrolases | IUPHAR Guide to IMMUNOPHARMACOLOGY

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vanin 1

  Target has curated data in GtoImmuPdb

Target id: 3063

Nomenclature: vanin 1

Family: Hydrolases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 513 6q23.2 VNN1 vanin 1 7
Mouse - 512 10 A4 Vnn1 vanin 1
Rat - 512 Vnn1 vanin 1
Previous and Unofficial Names
pantetheinase
Database Links
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Entrez Gene
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KEGG Gene
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RefSeq Protein
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Enzyme Reaction
EC Number: 3.5.1.92
Description Reaction Reference
Hydrolysis of pantothenic acid (vitamin B5) to release cysteamine (R)-pantetheine + H(2)O <=> (R)-pantothenate + 2-aminoethanethiol

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
example 25 [WO2018228934] Hs Inhibition 10.0 pIC50 5
pIC50 10.0 (IC50 1x10-10 M) [5]
Description: Measuring inhibition of pantothenic acid formation by test compound, as detected by RapidFire mass spectrometry.
Immunopharmacology Comments
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [13], systemic sclerosis [10] and colitis [3,9,12]. In murine models increased vanin 1 activity in the gut epithelium has been implicated in promoting tissue damage and inflammation by reducing resistance to oxidative stress [2-3,11-12]. Elevated vanin 1 expression has been detected in intestinal epithelium in tissue biopsies from ulcerative colitis and Crohn's disease patients and a gain-of-function polymorphism in VNN1 is associated with increased susceptibility to irritable bowel syndrome [8]. Based on this (and other) evidence pharmacological inhibition of vanin 1 is being explored as a novel mechanism for the treatment of inflammatory diseases [5-6].
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0033089 positive regulation of T cell differentiation in thymus ISS
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0033089 positive regulation of T cell differentiation in thymus ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0033089 positive regulation of T cell differentiation in thymus ISS
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0033089 positive regulation of T cell differentiation in thymus ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 5 GO processes
GO:0002526 acute inflammatory response ISS
GO:0002544 chronic inflammatory response ISS
GO:0006954 inflammatory response ISS
GO:0043312 neutrophil degranulation TAS
GO:0045087 innate immune response ISS
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0033089 positive regulation of T cell differentiation in thymus ISS
Tissue Distribution
Expressed in spleen, thymus, peripheral blood lymphocytes and small intestine
Species:  Human
Technique:  Northern blot
References:  7
Thymic perivascular cells (pericytes)
Species:  Mouse
Technique: 
References:  1
Physiological Consequences of Altering Gene Expression
Vanin-1 null mice exhibit a glutathione-mediated tissue resistance to oxidative stress.
Species:  Mouse
Tissue: 
Technique: 
References:  2
General Comments
Vanin 1 is a GPI-anchored enzyme that involved in leukocyte homing to the thymus [1] and links metabolic disease to inflammation [4,14]. Vanin 1-catalysed production of cysteamine has been linked to increased oxidative stress in tissues resulting from decreased glutathione levels. In murine models increased vanin 1 activity in the gut epithelium has been implicated in promoting tissue damage and inflammation by reducing resistance to oxidative stress [2-3,11-12].

References

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1. Aurrand-Lions M, Galland F, Bazin H, Zakharyev VM, Imhof BA, Naquet P. (1996) Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing. Immunity, 5 (5): 391-405. [PMID:8934567]

2. Berruyer C, Martin FM, Castellano R, Macone A, Malergue F, Garrido-Urbani S, Millet V, Imbert J, Duprè S, Pitari G et al.. (2004) Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Mol. Cell. Biol., 24 (16): 7214-24. [PMID:15282320]

3. Berruyer C, Pouyet L, Millet V, Martin FM, LeGoffic A, Canonici A, Garcia S, Bagnis C, Naquet P, Galland F. (2006) 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 (13): 2817-27. [PMID:17145956]

4. Boersma YL, Newman J, Adams TE, Cowieson N, Krippner G, Bozaoglu K, Peat TS. (2014) The structure of vanin 1: a key enzyme linking metabolic disease and inflammation. Acta Crystallogr. D Biol. Crystallogr., 70 (Pt 12): 3320-9. [PMID:25478849]

5. Bosanac T, Burke MJ, Cook BN, DiSalvo DT, Kirrane Jr TM, Shen Y. (2018) HETEROAROMATIC COMPOUNDS AS VANIN INHIBITORS. Patent number: WO2018228934. Assignee: BOEHRINGER INGELHEIM INTERNATIONAL GMBH. Priority date: 12/06/2017. Publication date: 20/12/2018.

6. Casimiro-Garcia A, Condon JS, Flick AC, Gopalsamy A, Kirincich SJ, Mathias JP, Strobach JW, Xiang JS, Xing LH, Wang X. (2018) Novel heterocyclic compounds as inhibitors of vanin-1 enzyme. Patent number: US20180148420A1. Assignee: Pfizer Inc. Priority date: 29/05/2015. Publication date: 31/05/2018.

7. Galland F, Malergue F, Bazin H, Mattei MG, Aurrand-Lions M, Theillet C, Naquet P. (1998) Two human genes related to murine vanin-1 are located on the long arm of human chromosome 6. Genomics, 53 (2): 203-13. [PMID:9790769]

8. Gensollen T, Bourges C, Rihet P, Rostan A, Millet V, Noguchi T, Bourdon V, Sobol H, Dubuquoy L, Bertin B et al.. (2013) Functional polymorphisms in the regulatory regions of the VNN1 gene are associated with susceptibility to inflammatory bowel diseases. Inflamm. Bowel Dis., 19 (11): 2315-25. [PMID:23949622]

9. Hosohata K, Ando H, Fujimura A. (2014) Early detection of renal injury using urinary vanin-1 in rats with experimental colitis. J Appl Toxicol, 34 (2): 184-90. [PMID:23307618]

10. Kavian N, Mehlal S, Marut W, Servettaz A, Giessner C, Bourges C, Nicco C, Chéreau C, Lemaréchal H, Dutilh MF et al.. (2016) Imbalance of the Vanin-1 Pathway in Systemic Sclerosis. J. Immunol., 197 (8): 3326-3335. [PMID:27647831]

11. Naquet P, Pitari G, Duprè S, Galland F. (2014) Role of the Vnn1 pantetheinase in tissue tolerance to stress. Biochem. Soc. Trans., 42 (4): 1094-100. [PMID:25110008]

12. Pouyet L, Roisin-Bouffay C, Clément A, Millet V, Garcia S, Chasson L, Issaly N, Rostan A, Hofman P, Naquet P et al.. (2010) Epithelial vanin-1 controls inflammation-driven carcinogenesis in the colitis-associated colon cancer model. Inflamm. Bowel Dis., 16 (1): 96-104. [PMID:19572375]

13. Sánchez-Muñoz F, Amezcua-Guerra LM, Macías-Palacios M, Márquez-Velasco R, Bojalil R. (2013) Vanin-1 as a potential novel biomarker for active nephritis in systemic lupus erythematosus. Lupus, 22 (3): 333-5. [PMID:23390193]

14. van Diepen JA, Jansen PA, Ballak DB, Hijmans A, Rutjes FP, Tack CJ, Netea MG, Schalkwijk J, Stienstra R. (2016) Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes. Sci Rep, 6: 21906. [PMID:26932716]

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