Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Enzyme Reaction
- Inhibitors
- Immunopharmacology Comments
- Immuno Process Associations
- Tissue Distribution
- Physiological Consequences of Altering Gene Expression
- Gene Expression and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- How to cite this page
Gene and Protein Information  |
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| 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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| Alphafold | O95497 (Hs) |
| BRENDA | 3.5.1.92 |
| ChEMBL Target | CHEMBL4739843 (Hs) |
| Ensembl Gene | ENSG00000112299 (Hs), ENSMUSG00000037440 (Mm), ENSRNOG00000016219 (Rn) |
| Entrez Gene | 8876 (Hs), 29142 (Mm), 29142 (Rn) |
| Human Protein Atlas | ENSG00000112299 (Hs) |
| KEGG Enzyme | 3.5.1.92 |
| KEGG Gene | hsa:8876 (Hs), mmu:29142 (Mm), rno:29142 (Rn) |
| OMIM | 603570 (Hs) |
| Pharos | O95497 (Hs) |
| RefSeq Nucleotide | NM_004666 (Hs), NM_011704 (Mm), NM_001025623 (Rn) |
| RefSeq Protein | NP_004657 (Hs), NP_035834 (Mm), NP_001020794 (Rn) |
| UniProtKB | O95497 (Hs) |
| Wikipedia | VNN1 (Hs) |
| Enzyme Reaction |
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Download all structure-activity data for this target as a CSV file 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||
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| Tissue Distribution
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| Physiological Consequences of Altering Gene Expression
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| Gene Expression and Pathophysiology Comments | |
| Vanin-1 expression is significantly increased in the colonic mucosa from IBD patients [8]. |
| Biologically Significant Variants
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| General Comments |
| Vanin 1 is a GPI-anchored enzyme that involved in leukocyte homing to the thymus [1] and links metabolic disease to inflammation [4,15]. 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
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. Unterschemmann K, Ehrmann A, Herzig I, Andreevski AL, Lustig K, Schmeck C, Eitner F, Grundmann M. (2021) Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease. Am J Physiol Renal Physiol, 320 (1): F61-F73. [PMID:33196323]
15. 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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