Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK1KG5W)

• DOT Name: Cyclin-Y (CCNY)
• Synonyms: Cyc-Y; Cyclin box protein 1; Cyclin fold protein 1; cyclin-X
• Gene Name: CCNY
• Related Disease:
  Gastric cancer
  Glioma
  Stomach cancer
  Type-1 diabetes
  Metastatic malignant neoplasm
  Neoplasm
  Lung carcinoma
  Ulcerative colitis
  Lung cancer
  Non-small-cell lung cancer
  Tuberculosis
  Adenocarcinoma
  Advanced cancer
  Clear cell adenocarcinoma
  Crohn disease
  Hepatocellular carcinoma
  Squamous cell carcinoma
• UniProt ID: CCNY_HUMAN
• Pfam ID: PF00134
• Sequence:
  MGNTTSCCVSSSPKLRRNAHSRLESYRPDTDLSREDTGCNLQHISDRENIDDLNMEFNPS
  DHPRASTIFLSKSQTDVREKRKSLFINHHPPGQIARKYSSCSTIFLDDSTVSQPNLKYTI
  KCVALAIYYHIKNRDPDGRMLLDIFDENLHPLSKSEVPPDYDKHNPEQKQIYRFVRTLFS
  AAQLTAECAIVTLVYLERLLTYAEIDICPANWKRIVLGAILLASKVWDDQAVWNVDYCQI
  LKDITVEDMNELERQFLELLQFNINVPSSVYAKYYFDLRSLAEANNLSFPLEPLSRERAH
  KLEAISRLCEDKYKDLRRSARKRSASADNLTLPRWSPAIIS
• Function: Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway. Recruits CDK16 to the plasma membrane. Isoform 3 might play a role in the activation of MYC-mediated transcription.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	moderate	Biomarker	[4]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[5]
Lung cancer	DISCM4YA	Disputed	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[4]
Tuberculosis	DIS2YIMD	Disputed	Altered Expression	[6]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]
Clear cell adenocarcinoma	DISYUGHZ	Limited	Biomarker	[9]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[11]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[7]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cyclin-Y (CCNY).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-Y (CCNY).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-Y (CCNY).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cyclin-Y (CCNY).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-Y (CCNY).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-Y (CCNY).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cyclin-Y (CCNY).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-Y (CCNY).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-Y (CCNY).	[20]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cyclin-Y (CCNY).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cyclin-Y (CCNY).	[22]

References

• [1] The survival analysis and oncogenic effects of CFP1 and 14-3-3 expression on gastric cancer.Cancer Cell Int. 2019 Aug 31;19:225. doi: 10.1186/s12935-019-0946-3. eCollection 2019.
• [2] Lentivirus-mediated knockdown of cyclin Y (CCNY) inhibits glioma cell proliferation.Oncol Res. 2010;18(8):359-64. doi: 10.3727/096504010x12644422320582.
• [3] Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects.Hum Mol Genet. 2010 May 15;19(10):2059-67. doi: 10.1093/hmg/ddq078. Epub 2010 Feb 22.
• [4] Establishing a detection method for CCNY: a potentially significant clinical investigative marker in NSCLC patients.Onco Targets Ther. 2019 Jan 29;12:921-932. doi: 10.2147/OTT.S180507. eCollection 2019.
• [5] Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.Nat Genet. 2011 Mar;43(3):246-52. doi: 10.1038/ng.764. Epub 2011 Feb 6.
• [6] Serum anti-CCNY autoantibody is an independent prognosis indicator for postoperative patients with early-stage nonsmall-cell lung carcinoma.Dis Markers. 2013;35(5):317-25. doi: 10.1155/2013/935943. Epub 2013 Sep 18.
• [7] Cell cycle protein cyclin Y is associated with human non-small-cell lung cancer proliferation and tumorigenesis.Clin Lung Cancer. 2011 Jan;12(1):43-50. doi: 10.3816/CLC.2011.n.006.
• [8] Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex.Exp Mol Med. 2019 Apr 16;51(4):1-17. doi: 10.1038/s12276-019-0242-2.
• [9] Identification of novel cyclin gene fusion transcripts in endometrioid ovarian carcinomas.Int J Cancer. 2018 Sep 15;143(6):1379-1387. doi: 10.1002/ijc.31418. Epub 2018 Apr 25.
• [10] Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis.Inflamm Bowel Dis. 2011 Sep;17(9):1936-42. doi: 10.1002/ibd.21579. Epub 2010 Dec 10.
• [11] Cyclin Y Modulates the Proliferation, Invasion, and Metastasis of Hepatocellular Carcinoma Cells.Med Sci Monit. 2018 Mar 20;24:1642-1653. doi: 10.12659/msm.906075.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [17] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [18] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [19] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.