Details of Drug Off-Target (DOT)

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

• DOT Name: CAP-Gly domain-containing linker protein 2 (CLIP2)
• Synonyms: Cytoplasmic linker protein 115; CLIP-115; Cytoplasmic linker protein 2; Williams-Beuren syndrome chromosomal region 3 protein; Williams-Beuren syndrome chromosomal region 4 protein
• Gene Name: CLIP2
• Related Disease:
  Advanced cancer
  AIDS-related lymphoma
  Breast carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Kaposi sarcoma
  Myotonic dystrophy
  Thyroid gland papillary carcinoma
  Autism
  Breast cancer
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Autoimmune polyendocrinopathy
  Cognitive impairment
  Hepatitis C virus infection
  Neoplasm
  Type-1 diabetes
• UniProt ID: CLIP2_HUMAN
• PDB ID: 2CP2; 2CP3
• Pfam ID: PF01302
• Sequence:
  MQKPSGLKPPGRGGKHSSPMGRTSTGSASSSAAVAASSKEGSPLHKQSSGPSSSPAAAAA
  PEKPGPKAAEVGDDFLGDFVVGERVWVNGVKPGVVQYLGETQFAPGQWAGVVLDDPVGKN
  DGAVGGVRYFECPALQGIFTRPSKLTRQPTAEGSGSDAHSVESLTAQNLSLHSGTATPPL
  TSRVIPLRESVLNSSVKTGNESGSNLSDSGSVKRGEKDLRLGDRVLVGGTKTGVVRYVGE
  TDFAKGEWCGVELDEPLGKNDGAVAGTRYFQCPPKFGLFAPIHKVIRIGFPSTSPAKAKK
  TKRMAMGVSALTHSPSSSSISSVSSVASSVGGRPSRSGLLTETSSRYARKISGTTALQEA
  LKEKQQHIEQLLAERDLERAEVAKATSHICEVEKEIALLKAQHEQYVAEAEEKLQRARLL
  VESVRKEKVDLSNQLEEERRKVEDLQFRVEEESITKGDLETQTQLEHARIGELEQSLLLE
  KAQAERLLRELADNRLTTVAEKSRVLQLEEELTLRRGEIEELQQCLLHSGPPPPDHPDAA
  EILRLRERLLSASKEHQRESGVLRDKYEKALKAYQAEVDKLRAANEKYAQEVAGLKDKVQ
  QATSENMGLMDNWKSKLDSLASDHQKSLEDLKATLNSGPGAQQKEIGELKAVMEGIKMEH
  QLELGNLQAKHDLETAMHVKEKEALREKLQEAQEELAGLQRHWRAQLEVQASQHRLELQE
  AQDQRRDAELRVHELEKLDVEYRGQAQAIEFLKEQISLAEKKMLDYERLQRAEAQGKQEV
  ESLREKLLVAENRLQAVEALCSSQHTHMIESNDISEETIRTKETVEGLQDKLNKRDKEVT
  ALTSQTEMLRAQVSALESKCKSGEKKVDALLKEKRRLEAELETVSRKTHDASGQLVLISQ
  ELLRKERSLNELRVLLLEANRHSPGPERDLSREVHKAEWRIKEQKLKDDIRGLREKLTGL
  DKEKSLSDQRRYSLIDRSSAPELLRLQHQLMSTEDALRDALDQAQQVEKLMEAMRSCPDK
  AQTIGNSGSANGIHQQDKAQKQEDKH
• Function: Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
AIDS-related lymphoma	DISSLRAU	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Kaposi sarcoma	DISC1H1Z	Strong	Biomarker	[6]
Myotonic dystrophy	DISNBEMX	Strong	Altered Expression	[7]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[8]
Autism	DISV4V1Z	moderate	Biomarker	[9]
Breast cancer	DIS7DPX1	moderate	Biomarker	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[10]
Liver cancer	DISDE4BI	moderate	Biomarker	[10]
Autoimmune polyendocrinopathy	DISOLDB2	Limited	Altered Expression	[11]
Cognitive impairment	DISH2ERD	Limited	Genetic Variation	[12]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[13]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[14]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[21]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[22]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[23]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[24]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of CAP-Gly domain-containing linker protein 2 (CLIP2).	[31]

3 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 decreases the methylation of CAP-Gly domain-containing linker protein 2 (CLIP2).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of CAP-Gly domain-containing linker protein 2 (CLIP2).	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the acetylation of CAP-Gly domain-containing linker protein 2 (CLIP2).	[32]

References

• [1] A Distributed Classifier for MicroRNA Target Prediction with Validation Through TCGA Expression Data.IEEE/ACM Trans Comput Biol Bioinform. 2018 Jul-Aug;15(4):1037-1051. doi: 10.1109/TCBB.2018.2828305. Epub 2018 Apr 19.
• [2] Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas. PLoS Pathog. 2012;8(8):e1002884.
• [3] HITS-CLIP reveals key regulators of nuclear receptor signaling in breast cancer. Breast Cancer Res Treat. 2014 Jul;146(1):85-97.
• [4] Monitoring the emergence of hepatitis B virus polymerase gene variants during lamivudine therapy in human immunodeficiency virus coinfected patients: performance of CLIP sequencing and line probe assay.Antivir Ther. 2003 Dec;8(6):627-34.
• [5] A combination of -fetoprotein, midkine, thioredoxin and a metabolite for predicting hepatocellular carcinoma.Ann Hepatol. 2020 Mar-Apr;19(2):179-185. doi: 10.1016/j.aohep.2019.09.002. Epub 2019 Oct 1.
• [6] HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.PLoS Pathog. 2015 Feb 24;11(2):e1004652. doi: 10.1371/journal.ppat.1004652. eCollection 2015 Feb.
• [7] MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain.Cell Rep. 2015 Aug 18;12(7):1159-68. doi: 10.1016/j.celrep.2015.07.029. Epub 2015 Aug 6.
• [8] Integration of a radiation biomarker into modeling of thyroid carcinogenesis and post-Chernobyl risk assessment.Carcinogenesis. 2016 Dec;37(12):1152-1160. doi: 10.1093/carcin/bgw102. Epub 2016 Oct 11.
• [9] HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism.Cell Rep. 2014 Mar 27;6(6):1139-1152. doi: 10.1016/j.celrep.2014.02.005. Epub 2014 Mar 6.
• [10] The Munich-Transarterial Chemoembolisation Score Holds Superior Prognostic Capacities Compared to TACE-Tailored Modifications of 9 Established Staging Systems for Hepatocellular Carcinoma.Digestion. 2019;100(1):15-26. doi: 10.1159/000493136. Epub 2018 Oct 3.
• [11] Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome.Blood. 2014 Dec 11;124(25):3808-16. doi: 10.1182/blood-2014-05-577569. Epub 2014 Oct 9.
• [12] Williams-Beuren syndrome: a model of recurrent genomic mutation.Horm Res. 2003;59 Suppl 1:106-13. doi: 10.1159/000067836.
• [13] Towards a better resolution of hepatitis C virus variants: CLIP sequencing of an HCV core fragment and automated assignment of genotypes and subtypes.J Virol Methods. 2008 Mar;148(1-2):25-33. doi: 10.1016/j.jviromet.2007.10.012. Epub 2007 Nov 28.
• [14] High Expression of FLOT1 Is Associated with Progression and Poor Prognosis in Hepatocellular Carcinoma.PLoS One. 2013 Jun 26;8(6):e64709. doi: 10.1371/journal.pone.0064709. Print 2013.
• [15] On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes.Expert Rev Mol Med. 2012 Jul 6;14:e15. doi: 10.1017/erm.2012.9.
• [16] 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.
• [17] 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.
• [18] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [19] 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.
• [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] 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.
• [22] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [23] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [24] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [25] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [26] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [32] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.