N-Acylethanolamine acid amidase
Target has curated data in GtoImmuPdb
Target id: 1402
Nomenclature: N-Acylethanolamine acid amidase
Abbreviated Name: NAAA
Family: N-Acylethanolamine turnover
Contents:
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 359 | 4q21.1 | NAAA | N-acylethanolamine acid amidase | |
| Mouse | - | 362 | 5 E2 | Naaa | N-acylethanolamine acid amidase | |
| Rat | - | 362 | 14p22 | Naaa | N-acylethanolamine acid amidase | |
| Previous and Unofficial Names |
| Acid ceramidase-like protein | N-palmitoylethanolamine acid amidase | ASAH-like protein | N-acylethanolamine-hydrolyzing acid amidase |
| Database Links |
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| Alphafold | Q02083 (Hs), Q9D7V9 (Mm), Q5KTC7 (Rn) |
| BRENDA | 3.5.1.- |
| ChEMBL Target | CHEMBL4349 (Hs), CHEMBL2034805 (Rn) |
| Ensembl Gene | ENSG00000138744 (Hs), ENSMUSG00000029413 (Mm), ENSRNOG00000002273 (Rn) |
| Entrez Gene | 27163 (Hs), 67111 (Mm), 497009 (Rn) |
| Human Protein Atlas | ENSG00000138744 (Hs) |
| KEGG Enzyme | 3.5.1.- |
| KEGG Gene | hsa:27163 (Hs), mmu:67111 (Mm), rno:497009 (Rn) |
| OMIM | 607469 (Hs) |
| Pharos | Q02083 (Hs) |
| UniProtKB | Q02083 (Hs), Q9D7V9 (Mm), Q5KTC7 (Rn) |
| Wikipedia | NAAA (Hs) |
| Selected 3D Structures |
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| Enzyme Reaction |
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| Rank order of affinity (Human) |
| N-palmitoylethanolamine > MEA > SEA ≥ N-oleoylethanolamide > anandamide [10] |
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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| Immunopharmacology Comments |
| NAAA is involved in the metabolism of fatty acid ethanolamides and endocannabinoids, which are endogenous ligands known to alleviate pain and inflammation [7]. It is located intracellularly in lysosomes of innate and adaptive immune cells, where it is activated at acidic pH. The molecular mechanism underlying activation of NAAA was revealed by X-ray crystallography [1]. NAAA catalyses the hydrolysis of short unsaturated N-acylethanolamines such as palmitoylethanolamide (PEA). PEA, as an agonist of peroxisome proliferator-activated receptor-α (PPARα), mediates a pro-inflammatory effect. Hydrolytic deactivation of PEA by NAAA reduces this PEA-PPARα activity. NAAA's function is in contrast to that of fatty acid amide hydrolase (FAAH) which preferentially degrades long-chain polyunsaturated N-acylethanolamine substrates, including anandamide. Pharmacological inhibition of NAAA, which induces an increase in fatty acid ethanolamides and endocannabinoids, is a therapeutic approach that is being investigated to enhance the antinociceptive and anti-inflammatory effects of these endogenous modulators [3-7,9]. |
References
1. Gorelik A, Gebai A, Illes K, Piomelli D, Nagar B. (2018) Molecular mechanism of activation of the immunoregulatory amidase NAAA. Proc Natl Acad Sci USA, 115 (43): E10032-E10040. [PMID:30301806]
2. Li Y, Chen Q, Yang L, Li Y, Zhang Y, Qiu Y, Ren J, Lu C. (2017) Identification of highly potent N-acylethanolamine acid amidase (NAAA) inhibitors: Optimization of the terminal phenyl moiety of oxazolidone derivatives. Eur J Med Chem, 139: 214-221. [PMID:28802121]
3. Li Y, Zhou P, Chen H, Chen Q, Kuang X, Lu C, Ren J, Qiu Y. (2018) Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid amidase (NAAA) inhibitor F215. Pharmacol Res, 132: 7-14. [PMID:29572189]
4. Migliore M, Pontis S, Fuentes de Arriba AL, Realini N, Torrente E, Armirotti A, Romeo E, Di Martino S, Russo D, Pizzirani D et al.. (2016) Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis. Angew Chem Int Ed Engl, 55 (37): 11193-7. [PMID:27404798]
5. Nuzzi A, Fiasella A, Ortega JA, Pagliuca C, Ponzano S, Pizzirani D, Bertozzi SM, Ottonello G, Tarozzo G, Reggiani A et al.. (2016) Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies. Eur J Med Chem, 111: 138-59. [PMID:26866968]
6. Petrosino S, Campolo M, Impellizzeri D, Paterniti I, Allarà M, Gugliandolo E, D'Amico R, Siracusa R, Cordaro M, Esposito E et al.. (2017) 2-Pentadecyl-2-Oxazoline, the Oxazoline of Pea, Modulates Carrageenan-Induced Acute Inflammation. Front Pharmacol, 8: 308. [PMID:28611664]
7. Piomelli D, Scalvini L, Fotio Y, Lodola A, Spadoni G, Tarzia G, Mor M. (2020) N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition. J Med Chem, 63 (14): 7475-7490. [PMID:32191459]
8. Ribeiro A, Pontis S, Mengatto L, Armirotti A, Chiurchiù V, Capurro V, Fiasella A, Nuzzi A, Romeo E, Moreno-Sanz G et al.. (2015) A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation. ACS Chem Biol, 10 (8): 1838-46. [PMID:25874594]
9. Tuo W, Leleu-Chavain N, Spencer J, Sansook S, Millet R, Chavatte P. (2017) Therapeutic Potential of Fatty Acid Amide Hydrolase, Monoacylglycerol Lipase, and N-Acylethanolamine Acid Amidase Inhibitors. J Med Chem, 60 (1): 4-46. [PMID:27766867]
10. Ueda N, Yamanaka K, Yamamoto S. (2001) Purification and characterization of an acid amidase selective for N-palmitoylethanolamine, a putative endogenous anti-inflammatory substance. J Biol Chem, 276 (38): 35552-7. [PMID:11463796]
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