Details of Drug Off-Target (DOT)

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

• DOT Name: CAP-Gly domain-containing linker protein 3 (CLIP3)
• Synonyms: Cytoplasmic linker protein 170-related 59 kDa protein; CLIP-170-related 59 kDa protein; CLIPR-59
• Gene Name: CLIP3
• UniProt ID: CLIP3_HUMAN
• PDB ID: 2CP0
• Pfam ID: PF12796 ; PF01302
• Sequence:
  MTKTDPAPMAPPPRGEEEEEEEEDEPVPEAPSPTQERRQKPVVHPSAPAPLPKDYAFTFF
  DPNDPACQEILFDPQTTIPELFAIVRQWVPQVQHKIDVIGNEILRRGCHVNDRDGLTDMT
  LLHYACKAGAHGVGDPAAAVRLSQQLLALGADVTLRSRWTNMNALHYAAYFDVPDLVRVL
  LKGARPRVVNSTCSDFNHGSALHIAASSLCLGAAKCLLEHGANPALRNRKGQVPAEVVPD
  PMDMSLDKAEAALVAKELRTLLEEAVPLSCALPKVTLPNYDNVPGNLMLSALGLRLGDRV
  LLDGQKTGTLRFCGTTEFASGQWVGVELDEPEGKNDGSVGGVRYFICPPKQGLFASVSKI
  SKAVDAPPSSVTSTPRTPRMDFSRVTGKGRREHKGKKKTPSSPSLGSLQQRDGAKAEVGD
  QVLVAGQKQGIVRFYGKTDFAPGYWYGIELDQPTGKHDGSVFGVRYFTCPPRHGVFAPAS
  RIQRIGGSTDSPGDSVGAKKVHQVTMTQPKRTFTTVRTPKDIASENSISRLLFCCWFPWM
  LRAEMQS
• Function: Functions as a cytoplasmic linker protein. Involved in TGN-endosome dynamics. May modulate the cellular compartmentalization of AKT kinase family and promote its cell membrane localization, thereby playing a role in glucose transport in adipocytes.
• Reactome Pathway: Regulation of TNFR1 signaling (R-HSA-5357905)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of CAP-Gly domain-containing linker protein 3 (CLIP3).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[7]
Aspirin	DM672AH	Approved	Aspirin increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[11]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[14]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of CAP-Gly domain-containing linker protein 3 (CLIP3).	[15]

References

• [1] 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.
• [2] 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.
• [3] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] 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.
• [6] 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.
• [7] Transcriptomic Analysis of Stem Cells Treated with Moringin or Cannabidiol: Analogies and Differences in Inflammation Pathways. Int J Mol Sci. 2019 Nov 30;20(23):6039. doi: 10.3390/ijms20236039.
• [8] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [11] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [12] Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma. Cancer Cell. 2017 Jan 9;31(1):50-63.
• [13] 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.
• [14] 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.
• [15] The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci. 2006 Sep;93(1):125-35. doi: 10.1093/toxsci/kfl046. Epub 2006 Jun 21.