Details of Drug Off-Target (DOT)

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

• DOT Name: Cytokine-like protein 1 (CYTL1)
• Synonyms: Protein C17
• Gene Name: CYTL1
• Related Disease:
  Arthritis
  Alcohol dependence
  Cardiac failure
  Congestive heart failure
  Lung squamous cell carcinoma
  Neoplasm
  Colorectal carcinoma
  Neuroblastoma
  Osteoarthritis
  Metastatic malignant neoplasm
• UniProt ID: CYTL1_HUMAN
• Pfam ID: PF15153
• Sequence:
  MRTPGPLPVLLLLLAGAPAARPTPPTCYSRMRALSQEITRDFNLLQVSEPSEPCVRYLPR
  LYLDIHNYCVLDKLRDFVASPPCWKVAQVDSLKDKARKLYTIMNSFCRRDLVFLLDDCNA
  LEYPIPVTTVLPDRQR
• Tissue Specificity: Specifically expressed in CD34+ hematopoietic cells.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Altered Expression	[1]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Lung squamous cell carcinoma	DISXPIBD	Strong	Posttranslational Modification	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[5]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[6]
Osteoarthritis	DIS05URM	moderate	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[6]

10 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 Cytokine-like protein 1 (CYTL1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytokine-like protein 1 (CYTL1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytokine-like protein 1 (CYTL1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cytokine-like protein 1 (CYTL1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cytokine-like protein 1 (CYTL1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cytokine-like protein 1 (CYTL1).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cytokine-like protein 1 (CYTL1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytokine-like protein 1 (CYTL1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytokine-like protein 1 (CYTL1).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cytokine-like protein 1 (CYTL1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cytokine-like protein 1 (CYTL1).	[15]

References

• [1] Biochemical and biophysical characterization of cytokine-like protein 1 (CYTL1).Cytokine. 2017 Aug;96:238-246. doi: 10.1016/j.cyto.2017.04.023. Epub 2017 May 4.
• [2] ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior.Chin Med J (Engl). 2012 Mar;125(6):1127-34.
• [3] Cytokine-Like 1 Regulates Cardiac Fibrosis via Modulation of TGF- Signaling.PLoS One. 2016 Nov 11;11(11):e0166480. doi: 10.1371/journal.pone.0166480. eCollection 2016.
• [4] Genome-wide analysis of DNA methylation and the gene expression change in lung cancer.J Thorac Oncol. 2012 Jan;7(1):20-33. doi: 10.1097/JTO.0b013e3182307f62.
• [5] Protein Cytl1: its role in chondrogenesis, cartilage homeostasis, and disease.Cell Mol Life Sci. 2019 Sep;76(18):3515-3523. doi: 10.1007/s00018-019-03137-x. Epub 2019 May 14.
• [6] CYTL1 inhibits tumor metastasis with decreasing STAT3 phosphorylation.Oncoimmunology. 2019 Feb 18;8(5):e1577126. doi: 10.1080/2162402X.2019.1577126. eCollection 2019.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [9] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [10] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] 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.
• [16] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [17] 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.