Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI9PMN1)

• DOT Name: Nuclear nucleic acid-binding protein C1D (C1D)
• Synonyms: hC1D
• Gene Name: C1D
• Related Disease:
  Alcohol dependence
  Arteriosclerosis
  Atherosclerosis
  Glioma
  Lung carcinoma
  Multiple sclerosis
  Osteoarthritis
  Thyroid gland carcinoma
  Thyroid gland follicular carcinoma
  Triple negative breast cancer
  Alcohol withdrawal
  Adult glioblastoma
  Alzheimer disease
  Autoimmune polyendocrinopathy
  Glioblastoma multiforme
  Lung adenocarcinoma
  Neuroblastoma
  Type-1/2 diabetes
• UniProt ID: C1D_HUMAN
• Pfam ID: PF04000
• Sequence:
  MAGEEINEDYPVEIHEYLSAFENSIGAVDEMLKTMMSVSRNELLQKLDPLEQAKVDLVSA
  YTLNSMFWVYLATQGVNPKEHPVKQELERIRVYMNRVKEITDKKKAGKLDRGAASRFVKN
  ALWEPKSKNASKVANKGKSKS
• Function: Plays a role in the recruitment of the RNA exosome complex to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA; this function may include MPHOSPH6. Can activate PRKDC not only in the presence of linear DNA but also in the presence of supercoiled DNA. Can induce apoptosis in a p53/TP53 dependent manner. May regulate the TRAX/TSN complex formation. Potentiates transcriptional repression by NR1D1 and THRB.
• Tissue Specificity: Ubiquitous. Expressed at very high levels in the hippocampus, medulla oblongata, mammary gland, thyroid and salivary gland. Expressed at high levels in the fetal; lung, liver and kidney. Expressed at low levels in skeletal muscle, appendix, heart, lung and colon.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[5]
Osteoarthritis	DIS05URM	Strong	Biomarker	[6]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[7]
Thyroid gland follicular carcinoma	DISFK2QT	Strong	Biomarker	[8]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[9]
Alcohol withdrawal	DIS7INCX	moderate	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[10]
Alzheimer disease	DISF8S70	Limited	Altered Expression	[11]
Autoimmune polyendocrinopathy	DISOLDB2	Limited	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[13]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[14]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Nuclear nucleic acid-binding protein C1D (C1D).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nuclear nucleic acid-binding protein C1D (C1D).	[17]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear nucleic acid-binding protein C1D (C1D).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear nucleic acid-binding protein C1D (C1D).	[19]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Nuclear nucleic acid-binding protein C1D (C1D).	[20]

References

• [1] Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.Pharmacol Rep. 2012;64(5):1126-34. doi: 10.1016/s1734-1140(12)70909-x.
• [2] Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation.Circ Res. 2019 Feb 15;124(4):e6-e19. doi: 10.1161/CIRCRESAHA.118.313028.
• [3] Design of multifunctional peptide collaborated and docetaxel loaded lipid nanoparticles for antiglioma therapy.Eur J Pharm Biopharm. 2018 Nov;132:168-179. doi: 10.1016/j.ejpb.2018.09.012. Epub 2018 Sep 20.
• [4] Cellular growth inhibition by IGFBP-3 and TGF-beta1 requires LRP-1.FASEB J. 2003 Nov;17(14):2068-81. doi: 10.1096/fj.03-0256com.
• [5] Selective upregulation of scavenger receptors in and around demyelinating areas in multiple sclerosis.J Neuropathol Exp Neurol. 2013 Feb;72(2):106-18. doi: 10.1097/NEN.0b013e31827fd9e8.
• [6] LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage.FASEB J. 2013 Feb;27(2):511-21. doi: 10.1096/fj.12-216671. Epub 2012 Oct 11.
• [7] Identification of LRP-1 as an endocytosis and recycling receptor for 1-integrin in thyroid cancer cells.Oncotarget. 2017 Aug 10;8(45):78614-78632. doi: 10.18632/oncotarget.20201. eCollection 2017 Oct 3.
• [8] Identification of a novel Rac3-interacting protein C1D.Int J Mol Med. 1998 Apr;1(4):665-70. doi: 10.3892/ijmm.1.4.665.
• [9] A gentle approach to investigate the influence of LRP-1 silencing on the migratory behavior of breast cancer cells by atomic force microscopy and dynamic cell studies.Nanomedicine. 2019 Jun;18:359-370. doi: 10.1016/j.nano.2018.10.012. Epub 2018 Nov 10.
• [10] Protein Toxin Chaperoned by LRP-1-Targeted Virus-Mimicking Vesicles Induces High-Efficiency Glioblastoma Therapy In Vivo.Adv Mater. 2018 Jul;30(30):e1800316. doi: 10.1002/adma.201800316. Epub 2018 Jun 11.
• [11] Astaxanthin exerts protective effects similar to bexarotene in Alzheimer's disease by modulating amyloid-beta and cholesterol homeostasis in blood-brain barrier endothelial cells.Biochim Biophys Acta Mol Basis Dis. 2019 Sep 1;1865(9):2224-2245. doi: 10.1016/j.bbadis.2019.04.019. Epub 2019 May 2.
• [12] The first genome-wide association study identifying new susceptibility loci for obstetric antiphospholipid syndrome.J Hum Genet. 2017 Sep;62(9):831-838. doi: 10.1038/jhg.2017.46. Epub 2017 Apr 20.
• [13] Genome-wide association study of familial lung cancer.Carcinogenesis. 2018 Sep 21;39(9):1135-1140. doi: 10.1093/carcin/bgy080.
• [14] NDRG1 promotes the multidrug resistance of neuroblastoma cells with upregulated expression of drug resistant proteins.Biomed Pharmacother. 2015 Dec;76:46-51. doi: 10.1016/j.biopha.2015.10.015. Epub 2015 Nov 10.
• [15] The Research on the Relationship of RAGE, LRP-1, and A Accumulation in the Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats.J Mol Neurosci. 2017 May;62(1):1-10. doi: 10.1007/s12031-017-0892-2. Epub 2017 Apr 11.
• [16] 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.
• [17] 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.
• [18] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [19] 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.
• [20] 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.