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Target has curated data in GtoImmuPdb
Target id: 2767
Nomenclature: amine oxidase copper containing 3
Abbreviated Name: VAP-1
Family: 1.-.-.- Oxidoreductases
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 763 | 17q21.31 | AOC3 | amine oxidase copper containing 3 | 14,17 |
Mouse | 1 | 765 | 11 D | Aoc3 | amine oxidase, copper containing 3 | |
Rat | 1 | 763 | 10q31 | Aoc3 | amine oxidase, copper containing 3 |
Previous and Unofficial Names |
amine oxidase | amine oxidase, copper containing 3 | HPAO | semicarbazide-sensitive amine oxidase | SSAO | VAP1 | vascular adhesion protein 1 |
Database Links | |
Alphafold | Q16853 (Hs), O70423 (Mm), O08590 (Rn) |
BRENDA | 1.4.3.21 |
CATH/Gene3D | 2.70.98.20 |
ChEMBL Target | CHEMBL3437 (Hs), CHEMBL4727 (Mm), CHEMBL4592 (Rn) |
DrugBank Target | Q16853 (Hs) |
Ensembl Gene | ENSG00000131471 (Hs), ENSMUSG00000019326 (Mm), ENSRNOG00000051307 (Rn) |
Entrez Gene | 8639 (Hs), 11754 (Mm), 29473 (Rn) |
Human Protein Atlas | ENSG00000131471 (Hs) |
KEGG Enzyme | 1.4.3.21 |
KEGG Gene | hsa:8639 (Hs), mmu:11754 (Mm), rno:29473 (Rn) |
OMIM | 03735 (Hs) |
Pharos | Q16853 (Hs) |
RefSeq Nucleotide | NM_003734 (Hs), NM_009675 (Mm), NM_031582 (Rn) |
RefSeq Protein | NP_003725 (Hs), NP_033805 (Mm), NP_113770 (Rn) |
UniProtKB | Q16853 (Hs), O70423 (Mm), O08590 (Rn) |
Wikipedia | AOC3 (Hs) |
Selected 3D Structures | |||||||||||
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Enzyme Reaction | ||||
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Download all structure-activity data for this target as a CSV file
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
As a membrane-bound glycoprotein AOC3 (a.k.a. SSAO, VAP-1) is expressed on the surface of endothelial cells when exposed to inflammatory conditions. It has been noted to mediate binding of lymphocytes to peripheral lymph node vascular endothelial cells, a process required for the recirculation of lymphocytes between blood and tissue. This activity profile has suggested AOC3 as a potential drug target for inflammatory and vascular diseases [10]. The clinical potential of AOC3 inhibitors is reviewed in a patent survey [3] and an Annual Reports in Medicinal Chemistry article [5]. |
Immuno Process Associations | ||
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Physiological Functions | ||||||||
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General Comments |
AOC3 (VAP-1) is a semicarbazide-sensitive amine oxidase, with substrate specificity which overlaps that of the monoamine oxidases (MAOs). AOC3 catalyzes the oxidative conversion of amines to aldehydes with copper and topaquinone (PubChem CID 12387) acting as cofactors. The enzyme is a membrane-bound glycoprotein. AOC3 is expressed on the surface of endothelial cells when exposed to inflammatory conditions [11] and has been noted to mediate binding of lymphocytes to peripheral lymph node vascular endothelial cells [8-9,12], a process required for the recirculation of lymphocytes between blood and tissue. This activity profile has suggested AOC3 as a potential drug target for inflammatory and vascular diseases. Specific and reversible inhibitors of AOC3 activity are in development [2,7,16], including the small molecule phenelzine and the mAb timolumab. |
1. Airenne TT, Nymalm Y, Kidron H, Smith DJ, Pihlavisto M, Salmi M, Jalkanen S, Johnson MS, Salminen TA. (2005) Crystal structure of the human vascular adhesion protein-1: unique structural features with functional implications. Protein Sci, 14 (8): 1964-74. [PMID:16046623]
2. Bligt-Lindén E, Pihlavisto M, Szatmári I, Otwinowski Z, Smith DJ, Lázár L, Fülöp F, Salminen TA. (2013) Novel pyridazinone inhibitors for vascular adhesion protein-1 (VAP-1): old target-new inhibition mode. J Med Chem, 56 (24): 9837-48. [PMID:24304424]
3. Dunkel P, Balogh B, Meleddu R, Maccioni E, Gyires K, Mátyus P. (2011) Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1: a patent survey. Expert Opin Ther Pat, 21 (9): 1453-71. [PMID:21675926]
4. Foot JS, Yow TT, Schilter H, Buson A, Deodhar M, Findlay AD, Guo L, McDonald IA, Turner CI, Zhou W et al.. (2013) PXS-4681A, a potent and selective mechanism-based inhibitor of SSAO/VAP-1 with anti-inflammatory effects in vivo. J Pharmacol Exp Ther, 347 (2): 365-74. [PMID:23943052]
5. McDonald IA, Foot JS, Yin P, Fleming E, van Dam EM. (2007) Semicarbazide-sensitive amine oxidase and vascular adhesion protein-1: One protein being validated as a therapeutic target for inflammatory diseases. Annu Rep Med Chem, 42: 229–243.
6. Nurminen EM, Pihlavisto M, Lázár L, Szakonyi Z, Pentikäinen U, Fülöp F, Pentikäinen OT. (2010) Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhesion protein-1. J Med Chem, 53 (17): 6301-15. [PMID:20690686]
7. O'Rourke AM, Wang EY, Miller A, Podar EM, Scheyhing K, Huang L, Kessler C, Gao H, Ton-Nu HT, Macdonald MT et al.. (2008) Anti-inflammatory effects of LJP 1586 [Z-3-fluoro-2-(4-methoxybenzyl)allylamine hydrochloride], an amine-based inhibitor of semicarbazide-sensitive amine oxidase activity. J Pharmacol Exp Ther, 324 (2): 867-75. [PMID:17993604]
8. Salmi M, Jalkanen S. (1992) A 90-kilodalton endothelial cell molecule mediating lymphocyte binding in humans. Science, 257 (5075): 1407-9. [PMID:1529341]
9. Salmi M, Jalkanen S. (1996) Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells. J Exp Med, 183 (2): 569-79. [PMID:8627168]
10. Salmi M, Jalkanen S. (2001) VAP-1: an adhesin and an enzyme. Trends Immunol, 22 (4): 211-6. [PMID:11274927]
11. Salmi M, Kalimo K, Jalkanen S. (1993) Induction and function of vascular adhesion protein-1 at sites of inflammation. J Exp Med, 178 (6): 2255-60. [PMID:8245796]
12. Salmi M, Rajala P, Jalkanen S. (1997) Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion. J Clin Invest, 99 (9): 2165-72. [PMID:9151788]
13. Schilter HC, Collison A, Russo RC, Foot JS, Yow TT, Vieira AT, Tavares LD, Mattes J, Teixeira MM, Jarolimek W. (2015) Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration. Respir Res, 16: 42. [PMID:25889951]
14. Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S. (1998) Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp Med, 188 (1): 17-27. [PMID:9653080]
15. Smith DJ, Vainio P, Mikkola J, Vuorio P, Vainio J. (2011) Fully human anti-VAP-1 monoclonal antibodies. Patent number: US7897149 B2. Assignee: Biotie Therapies Corp.. Priority date: 20/04/2007. Publication date: 01/03/2011.
16. Wang EY, Gao H, Salter-Cid L, Zhang J, Huang L, Podar EM, Miller A, Zhao J, O'rourke A, Linnik MD. (2006) Design, synthesis, and biological evaluation of semicarbazide-sensitive amine oxidase (SSAO) inhibitors with anti-inflammatory activity. J Med Chem, 49 (7): 2166-73. [PMID:16570912]
17. Zhang X, McIntire WS. (1996) Cloning and sequencing of a copper-containing, topa quinone-containing monoamine oxidase from human placenta. Gene, 179 (2): 279-86. [PMID:8972912]
1.-.-.- Oxidoreductases: amine oxidase copper containing 3. Last modified on 27/03/2019. Accessed on 02/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2767.