Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS2PQ0O)

DOT Name N-acylethanolamine-hydrolyzing acid amidase (NAAA)
Synonyms EC 3.5.1.60; Acid ceramidase-like protein; Acylsphingosine deacylase NAAA; EC 3.5.1.23; N-acylsphingosine amidohydrolase-like; ASAH-like protein
Gene Name NAAA
UniProt ID
NAAA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6DXW; 6DXX
EC Number
3.5.1.23; 3.5.1.60
Pfam ID
PF02275 ; PF15508
Sequence
MRTADREARPGLPSLLLLLLAGAGLSAASPPAAPRFNVSLDSVPELRWLPVLRHYDLDLV
RAAMAQVIGDRVPKWVHVLIGKVVLELERFLPQPFTGEIRGMCDFMNLSLADCLLVNLAY
ESSVFCTSIVAQDSRGHIYHGRNLDYPFGNVLRKLTVDVQFLKNGQIAFTGTTFIGYVGL
WTGQSPHKFTVSGDERDKGWWWENAIAALFRRHIPVSWLIRATLSESENFEAAVGKLAKT
PLIADVYYIVGGTSPREGVVITRNRDGPADIWPLDPLNGAWFRVETNYDHWKPAPKEDDR
RTSAIKALNATGQANLSLEALFQILSVVPVYNNFTIYTTVMSAGSPDKYMTRIRNPSRK
Function
Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N-lauroylsphingosine and N-palmitoylsphingosine.
Tissue Specificity Expressed in numerous tissues, with highest levels in liver and kidney, followed by pancreas.
Reactome Pathway
Neurotransmitter release cycle (R-HSA-112310 )
BioCyc Pathway
MetaCyc:ENSG00000138744-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [4]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [5]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [6]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [7]
Triclosan DMZUR4N Approved Triclosan decreases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [8]
Progesterone DMUY35B Approved Progesterone increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [9]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA). [12]
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⏷ Show the Full List of 12 Drug(s)

References

1 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
2 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
6 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
7 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
8 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9 Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
10 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
11 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
12 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.