Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6YCNLF)

• DOT Name: Coactosin-like protein (COTL1)
• Gene Name: COTL1
• Related Disease:
  Isolated Pierre-Robin syndrome
  Alzheimer disease
  Alzheimer disease 3
  Autoimmune disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cleft soft palate
  Colitis
  Colon cancer
  Colon carcinoma
  Epilepsy
  Glioma
  Lung neoplasm
  Metastatic malignant neoplasm
  Neoplasm
  Obstructive lung disease
  Oral lichen planus
  Osteosarcoma
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Triple negative breast cancer
  Small-cell lung cancer
  Dental caries
  Non-small-cell lung cancer
• UniProt ID: COTL1_HUMAN
• PDB ID: 1T2L; 1T3X; 1T3Y; 1TMW; 1VFQ; 1WNJ
• Pfam ID: PF00241
• Sequence:
  MATKIDKEACRAAYNLVRDDGSAVIWVTFKYDGSTIVPGEQGAEYQHFIQQCTDDVRLFA
  FVRFTTGDAMSKRSKFALITWIGENVSGLQRAKTGTDKTLVKEVVQNFAKEFVISDRKEL
  EEDFIKSELKKAGGANYDAQTE
• Function: Binds to F-actin in a calcium-independent manner. Has no direct effect on actin depolymerization. Acts as a chaperone for ALOX5 (5LO), influencing both its stability and activity in leukotrienes synthesis.
• Tissue Specificity: Widely expressed with highest levels in placenta, lung, kidney and peripheral blood leukocytes and lower levels in brain, liver and pancreas.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated Pierre-Robin syndrome	DISVEHG7	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Cleft soft palate	DISCN11I	Strong	Biomarker	[7]
Colitis	DISAF7DD	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Genetic Variation	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Lung neoplasm	DISVARNB	Strong	Biomarker	[11]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Obstructive lung disease	DIS4IIDZ	Strong	Biomarker	[13]
Oral lichen planus	DISVEAJA	Strong	Biomarker	[3]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[14]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[14]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[15]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[16]
Dental caries	DISRBCMD	Limited	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[18]

20 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 Coactosin-like protein (COTL1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coactosin-like protein (COTL1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Coactosin-like protein (COTL1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Coactosin-like protein (COTL1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coactosin-like protein (COTL1).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Coactosin-like protein (COTL1).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Coactosin-like protein (COTL1).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coactosin-like protein (COTL1).	[26]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coactosin-like protein (COTL1).	[27]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Coactosin-like protein (COTL1).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Coactosin-like protein (COTL1).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Coactosin-like protein (COTL1).	[30]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Coactosin-like protein (COTL1).	[31]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Coactosin-like protein (COTL1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coactosin-like protein (COTL1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Coactosin-like protein (COTL1).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coactosin-like protein (COTL1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coactosin-like protein (COTL1).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Coactosin-like protein (COTL1).	[36]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Coactosin-like protein (COTL1).	[37]

References

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• [4] The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line.Int J Oncol. 2007 Oct;31(4):915-22.
• [5] Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGF signaling.Oncogene. 2018 Jan 18;37(3):323-331. doi: 10.1038/onc.2017.342. Epub 2017 Sep 18.
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• [11] Selective Cell Penetrating Peptide-Functionalized Envelope-Type Chimeric Lipopepsomes Boost Systemic RNAi Therapy for Lung Tumors.Adv Healthc Mater. 2019 Aug;8(16):e1900500. doi: 10.1002/adhm.201900500. Epub 2019 Jun 24.
• [12] Differential expression of PAI-RBP1, C1orf142, and COTL1 in non-small cell lung cancer cell lines with different tumor metastatic potential.J Investig Med. 2012 Apr;60(4):689-94. doi: 10.2310/JIM.0b013e31824963b6.
• [13] An algorithm for predicting Robin sequence from fetal MRI.Prenat Diagn. 2018 Apr;38(5):357-364. doi: 10.1002/pd.5239. Epub 2018 Mar 13.
• [14] Polymorphisms of COTL1 gene identified by proteomic approach and their association with autoimmune disorders.Exp Mol Med. 2009 May 31;41(5):354-61. doi: 10.3858/emm.2009.41.5.040.
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• [16] Proteomic analysis of human small cell lung cancer tissues: up-regulation of coactosin-like protein-1.J Proteome Res. 2011 Jan 7;10(1):269-76. doi: 10.1021/pr100714b. Epub 2010 Dec 2.
• [17] Antibacterial and Antibiofilm Activities of a Novel Synthetic Cyclic Lipopeptide against Cariogenic Streptococcus mutans UA159.Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00776-17. doi: 10.1128/AAC.00776-17. Print 2017 Aug.
• [18] Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression.Oncotarget. 2017 Jan 3;8(1):644-657. doi: 10.18632/oncotarget.13501.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [21] 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.
• [22] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
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• [24] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [25] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [26] 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.
• [27] 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.
• [28] 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.
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• [30] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [31] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [32] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [33] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [34] 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.
• [35] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [36] 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.
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