Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVSYP2D)

• DOT Name: Nocturnin (NOCT)
• Synonyms: EC 3.1.3.108; Carbon catabolite repression 4-like protein
• Gene Name: NOCT
• Related Disease:
  Neoplasm
  T-cell lymphoma
  Tuberculosis
  Adult lymphoma
  Alzheimer disease
  Angioimmunoblastic T-cell Lymphoma
  Breast carcinoma
  Breast neoplasm
  Fatty liver disease
  Idiopathic hypereosinophilic syndrome
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Lung squamous cell carcinoma
  Lymphoma
  Non-small-cell lung cancer
  Parkinson disease
  Pediatric lymphoma
  Sarcoidosis
  Small-cell lung cancer
  Dental caries
  Neuroendocrine neoplasm
  Obesity
• UniProt ID: NOCT_HUMAN
• PDB ID: 6BT1; 6BT2; 6MAL; 6NF0
• EC Number: 3.1.3.108
• Pfam ID: PF03372
• Sequence:
  MFHSPRRLCSALLQRDAPGLRRLPAPGLRRPLSPPAAVPRPASPRLLAAASAASGAARSC
  SRTVCSMGTGTSRLYSALAKTLNSSAASQHPEYLVSPDPEHLEPIDPKELLEECRAVLHT
  RPPRFQRDFVDLRTDCPSTHPPIRVMQWNILAQALGEGKDNFVQCPVEALKWEERKCLIL
  EEILAYQPDILCLQEVDHYFDTFQPLLSRLGYQGTFFPKPWSPCLDVEHNNGPDGCALFF
  LQNRFKLVNSANIRLTAMTLKTNQVAIAQTLECKESGRQFCIAVTHLKARTGWERFRSAQ
  GCDLLQNLQNITQGAKIPLIVCGDFNAEPTEEVYKHFASSSLNLNSAYKLLSADGQSEPP
  YTTWKIRTSGECRHTLDYIWYSKHALNVRSALDLLTEEQIGPNRLPSFNYPSDHLSLVCD
  FSFTEESDGLS
• Function: Phosphatase which catalyzes the conversion of NADP(+) to NAD(+) and of NADPH to NADH. Shows a small preference for NADPH over NADP(+). Represses translation and promotes degradation of target mRNA molecules. Plays an important role in post-transcriptional regulation of metabolic genes under circadian control. Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis. Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance. Promotes adipogenesis by facilitating PPARG nuclear translocation which activates its transcriptional activity. Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone. Critical for proper development of early embryos.
• Tissue Specificity: Adipose tissue. Expression is higher in subcutaneous adipose tissue as compared to visceral adipose tissue.
• Reactome Pathway: BMAL1 (R-HSA-1368108)
• BioCyc Pathway: MetaCyc:ENSG00000151014-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
T-cell lymphoma	DISSXRTQ	Definitive	Biomarker	[2]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[3]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Angioimmunoblastic T-cell Lymphoma	DISZPFTL	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[7]
Idiopathic hypereosinophilic syndrome	DISXAPO9	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[9]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[9]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[10]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[11]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[9]
Parkinson disease	DISQVHKL	Strong	Biomarker	[5]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[4]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[12]
Small-cell lung cancer	DISK3LZD	Strong	Genetic Variation	[4]
Dental caries	DISRBCMD	Limited	Biomarker	[13]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[6]
Obesity	DIS47Y1K	Limited	Altered Expression	[14]

16 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 Nocturnin (NOCT).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nocturnin (NOCT).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nocturnin (NOCT).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nocturnin (NOCT).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nocturnin (NOCT).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nocturnin (NOCT).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nocturnin (NOCT).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nocturnin (NOCT).	[22]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Nocturnin (NOCT).	[23]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nocturnin (NOCT).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nocturnin (NOCT).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nocturnin (NOCT).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nocturnin (NOCT).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nocturnin (NOCT).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nocturnin (NOCT).	[28]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Nocturnin (NOCT).	[29]

References

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• [5] Reducing INS-IGF1 signaling protects against non-cell autonomous vesicle rupture caused by SNCA spreading.Autophagy. 2020 May;16(5):878-899. doi: 10.1080/15548627.2019.1643657. Epub 2019 Jul 29.
• [6] Incidental finding of a breast carcinoma on Ga-68-DOTA-1-Nal3-octreotide positron emission tomography/computed tomography performed for the evaluation of a pancreatic neuroendocrine tumor: A case report.Medicine (Baltimore). 2018 Sep;97(36):e11878. doi: 10.1097/MD.0000000000011878.
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• [9] Association between CLOCK, PER3 and CCRN4L with nonsmall cell lung cancer in Brazilian patients.Mol Med Rep. 2014 Jul;10(1):435-40. doi: 10.3892/mmr.2014.2224. Epub 2014 May 8.
• [10] RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4.Clin Exp Metastasis. 2006;23(1):9-18. doi: 10.1007/s10585-006-9006-1. Epub 2006 Jul 5.
• [11] Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression.Mol Cancer. 2015 Nov 5;14:187. doi: 10.1186/s12943-015-0457-3.
• [12] Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis.Nucl Med Commun. 2018 Aug;39(8):768-778. doi: 10.1097/MNM.0000000000000869.
• [13] Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells.Sci Rep. 2018 Feb 21;8(1):3419. doi: 10.1038/s41598-018-21183-6.
• [14] Temporal Control of Metabolic Amplitude by Nocturnin.Cell Rep. 2018 Jan 30;22(5):1225-1235. doi: 10.1016/j.celrep.2018.01.011.
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• [17] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [18] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [21] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [22] 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.
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• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] 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.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.