Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOVXA2)

• DOT Name: Centriolar coiled-coil protein of 110 kDa (CCP110)
• Synonyms: Centrosomal protein of 110 kDa; CP110; Cep110
• Gene Name: CCP110
• Related Disease:
  Lung cancer
  Myeloproliferative neoplasm
  Neoplasm
  Lung carcinoma
• UniProt ID: CP110_HUMAN
• Pfam ID: PF16025
• Sequence:
  MEEYEKFCEKSLARIQEASLSTESFLPAQSESISLIRFHGVAILSPLLNIEKRKEMQQEK
  QKALDVEARKQVNRKKALLTRVQEILDNVQVRKAPNASDFDQWEMETVYSNSEVRNLNVP
  ATFPNSFPSHTEHSTAAKLDKIAGILPLDNEDQCKTDGIDLARDSEGFNSPKQCDSSNIS
  HVENEAFPKTSSATPQETLISDGPFSVNEQQDLPLLAEVIPDPYVMSLQNLMKKSKEYIE
  REQSRRSLRGSINRIVNESHLDKEHDAVEVADCVKEKGQLTGKHCVSVIPDKPSLNKSNV
  LLQGASTQASSMSMPVLASFSKVDIPIRTGHPTVLESNSDFKVIPTFVTENNVIKSLTGS
  YAKLPSPEPSMSPKMHRRRSRTSSACHILINNPINACELSPKGKEQAMDLIIQDTDENTN
  VPEIMPKLPTDLAGVCSSKVYVGKNTSEVKEDVVLGKSNQVCQSSGNHLENKVTHGLVTV
  EGQLTSDERGAHIMNSTCAAMPKLHEPYASSQCIASPNFGTVSGLKPASMLEKNCSLQTE
  LNKSYDVKNPSPLLMQNQNTRQQMDTPMVSCGNEQFLDNSFEKVKRRLDLDIDGLQKENC
  PYVITSGITEQERQHLPEKRYPKGSGFVNKNKMLGTSSKESEELLKSKMLAFEEMRKRLE
  EQHAQQLSLLIAEQEREQERLQKEIEEQEKMLKEKKAMTAEASELDINNAVELEWRKISD
  SSLLETMLSQADSLHTSNSNSSGFTNSAMQYSFVSANEAPFYLWGSSTSGLTKLSVTRPF
  GRAKTRWSQVFSLEIQAKFNKITAVAKGFLTRRLMQTDKLKQLRQTVKDTMEFIRSFQSE
  APLKRGIVSAQDASLQERVLAQLRAALYGIHDIFFVMDAAERMSILHHDREVRKEKMLRQ
  MDKMKSPRVALSAATQKSLDRKKYMKAAEMGMPNKKFLVKQNPSETRVLQPNQGQNAPVH
  RLLSRQGTPKTSVKGVVQNRQKPSQSRVPNRVPVSGVYAGKIQRKRPNVATI
• Function: Necessary for centrosome duplication at different stages of procentriole formation. Acts as a key negative regulator of ciliogenesis in collaboration with CEP97 by capping the mother centriole thereby preventing cilia formation. Also involved in promoting ciliogenesis. May play a role in the assembly of the mother centriole subdistal appendages (SDA) thereby effecting the fusion of recycling endosomes to basal bodies during cilia formation. Required for correct spindle formation and has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CETN2.
• Tissue Specificity: Highly expressed in testis. Detected at intermediate levels in spleen, thymus, prostate, small intestine, colon and peripheral blood leukocytes.
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  Ub-specific processing proteases (R-HSA-5689880)
  AURKA Activation by TPX2 (R-HSA-8854518)
  RHOV GTPase cycle (R-HSA-9013424)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[1]

13 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 Centriolar coiled-coil protein of 110 kDa (CCP110).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Centriolar coiled-coil protein of 110 kDa (CCP110).	[15]

References

• [1] CDK2 Inhibition Causes Anaphase Catastrophe in Lung Cancer through the Centrosomal Protein CP110.Cancer Res. 2015 May 15;75(10):2029-38. doi: 10.1158/0008-5472.CAN-14-1494. Epub 2015 Mar 25.
• [2] NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.Cancer Res. 2004 Apr 15;64(8):2673-6. doi: 10.1158/0008-5472.can-04-0144.
• [3] Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network.J Biol Chem. 2016 Aug 26;291(35):18496-504. doi: 10.1074/jbc.M116.739771. Epub 2016 Jul 8.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] 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.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.