Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUBJ7SX)

DOT Name Serotonin N-acetyltransferase (AANAT)
Synonyms Serotonin acetylase; EC 2.3.1.87; Aralkylamine N-acetyltransferase; AA-NAT
Gene Name AANAT
Related Disease
Oral lichen planus ( )
Advanced cancer ( )
Androgen insensitivity syndrome ( )
Autism spectrum disorder ( )
Bipolar depression ( )
Breast cancer ( )
Breast carcinoma ( )
Cholestasis ( )
Colorectal carcinoma ( )
Depression ( )
Major depressive disorder ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Retinoblastoma ( )
Sleep-wake disorder ( )
Adrenocortical insufficiency ( )
Melanoma ( )
Asthma ( )
UniProt ID
SNAT_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6T80
EC Number
2.3.1.87
Pfam ID
PF00583
Sequence
MSTQSTHPLKPEAPRLPPGIPESPSCQRRHTLPASEFRCLTPEDAVSAFEIEREAFISVL
GVCPLYLDEIRHFLTLCPELSLGWFEEGCLVAFIIGSLWDKERLMQESLTLHRSGGHIAH
LHVLAVHRAFRQQGRGPILLWRYLHHLGSQPAVRRAALMCEDALVPFYERFSFHAVGPCA
ITVGSLTFMELHCSLRGHPFLRRNSGC
Function Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin.
Tissue Specificity Highly expressed in pineal gland and at lower levels in the retina. Weak expression in several brain regions and in the pituitary gland.
KEGG Pathway
Tryptophan metabolism (hsa00380 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Serotonin and melatonin biosynthesis (R-HSA-209931 )
BioCyc Pathway
MetaCyc:HS05303-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Oral lichen planus DISVEAJA Definitive Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Androgen insensitivity syndrome DISUZBBO Strong Genetic Variation [3]
Autism spectrum disorder DISXK8NV Strong Biomarker [4]
Bipolar depression DISA75FU Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Genetic Variation [6]
Breast carcinoma DIS2UE88 Strong Genetic Variation [6]
Cholestasis DISDJJWE Strong Altered Expression [7]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Depression DIS3XJ69 Strong Biomarker [8]
Major depressive disorder DIS4CL3X Strong Genetic Variation [5]
Neoplasm DISZKGEW Strong Altered Expression [2]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [9]
Retinoblastoma DISVPNPB Strong Biomarker [10]
Sleep-wake disorder DISOBM0Q Strong Biomarker [11]
Adrenocortical insufficiency DISZ0CPT moderate Altered Expression [12]
Melanoma DIS1RRCY moderate Biomarker [13]
Asthma DISW9QNS Limited Biomarker [14]
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⏷ Show the Full List of 18 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Serotonin N-acetyltransferase (AANAT). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Serotonin N-acetyltransferase (AANAT). [16]
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References

1 Increased melatonin in oral mucosal tissue of oral lichen planus (OLP) patients: A possible link between melatonin and its role in oral mucosal inflammation.Arch Oral Biol. 2017 Jun;78:13-19. doi: 10.1016/j.archoralbio.2017.02.007. Epub 2017 Feb 6.
2 AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors.Int J Mol Sci. 2017 Jun 11;18(6):1251. doi: 10.3390/ijms18061251.
3 Association study of tryptophan hydroxylase 1 and arylalkylamine N-acetyltransferase polymorphisms with adolescent idiopathic scoliosis in Han Chinese.Spine (Phila Pa 1976). 2008 Sep 15;33(20):2199-203. doi: 10.1097/BRS.0b013e31817c03f9.
4 Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders.Sci Rep. 2017 May 18;7(1):2096. doi: 10.1038/s41598-017-02152-x.
5 Resequencing and association analysis of arylalkylamine N-acetyltransferase (AANAT) gene and its contribution to major depression susceptibility.J Pineal Res. 2010 Aug;49(1):35-44. doi: 10.1111/j.1600-079X.2010.00763.x. Epub 2010 Apr 29.
6 Polymorphisms in circadian genes, night work and breast cancer: results from the GENICA study.Chronobiol Int. 2014 Dec;31(10):1115-22. doi: 10.3109/07420528.2014.957301. Epub 2014 Sep 17.
7 Pinealectomy or light exposure exacerbates biliary damage and liver fibrosis in cholestatic rats through decreased melatonin synthesis.Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1525-1539. doi: 10.1016/j.bbadis.2019.03.002. Epub 2019 Mar 16.
8 Prolonged swim-test immobility of serotonin N-acetyltransferase (AANAT)-mutant mice.J Pineal Res. 2001 Apr;30(3):166-70. doi: 10.1034/j.1600-079x.2001.300305.x.
9 Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status.J Pineal Res. 2006 Mar;40(2):135-43. doi: 10.1111/j.1600-079X.2005.00287.x.
10 Regulation of AA-NAT and HIOMT gene expression by butyrate and cyclic AMP in Y79 human retinoblastoma cells.J Pineal Res. 1999 Sep;27(2):116-21. doi: 10.1111/j.1600-079x.1999.tb00605.x.
11 Significant association of the arylalkylamine N-acetyltransferase ( AA-NAT) gene with delayed sleep phase syndrome.Neurogenetics. 2003 Apr;4(3):151-3. doi: 10.1007/s10048-002-0141-9. Epub 2002 Nov 29.
12 Circadian Rhythm of Glucocorticoid Administration Entrains Clock Genes in Immune Cells: A DREAM Trial Ancillary Study.J Clin Endocrinol Metab. 2018 Aug 1;103(8):2998-3009. doi: 10.1210/jc.2018-00346.
13 Running for time: circadian rhythms and melanoma.Tumour Biol. 2014 Sep;35(9):8359-68. doi: 10.1007/s13277-014-1904-2. Epub 2014 Apr 14.
14 N-acetyltransferases as markers for asthma and allergic/atopic disorders.Curr Drug Metab. 2008 Jul;9(6):546-53. doi: 10.2174/138920008784892074.
15 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
16 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.