Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK61F2A)

• DOT Name: Plastin-2 (LCP1)
• Synonyms: L-plastin; LC64P; Lymphocyte cytosolic protein 1; LCP-1
• Gene Name: LCP1
• Related Disease:
  B-cell neoplasm
  Lung cancer
  Lung carcinoma
  Prostate cancer
  Prostate carcinoma
  Coloboma
  Colonic neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Malignant soft tissue neoplasm
  Melanoma
  Myocardial infarction
  Neoplasm
  Nicotine dependence
  Non-alcoholic fatty liver disease
  Oral cancer
  Ovarian cancer
  Ovarian neoplasm
  Retinoblastoma
  Sarcoma
  Type-1/2 diabetes
  Small lymphocytic lymphoma
  Advanced cancer
  Systemic lupus erythematosus
• UniProt ID: PLSL_HUMAN
• PDB ID: 2D85; 5JOJ; 5JOL; 6VEC
• Pfam ID: PF00307 ; PF13499
• Sequence:
  MARGSVSDEEMMELREAFAKVDTDGNGYISFNELNDLFKAACLPLPGYRVREITENLMAT
  GDLDQDGRISFDEFIKIFHGLKSTDVAKTFRKAINKKEGICAIGGTSEQSSVGTQHSYSE
  EEKYAFVNWINKALENDPDCRHVIPMNPNTNDLFNAVGDGIVLCKMINLSVPDTIDERTI
  NKKKLTPFTIQENLNLALNSASAIGCHVVNIGAEDLKEGKPYLVLGLLWQVIKIGLFADI
  ELSRNEALIALLREGESLEDLMKLSPEELLLRWANYHLENAGCNKIGNFSTDIKDSKAYY
  HLLEQVAPKGDEEGVPAVVIDMSGLREKDDIQRAECMLQQAERLGCRQFVTATDVVRGNP
  KLNLAFIANLFNRYPALHKPENQDIDWGALEGETREERTFRNWMNSLGVNPRVNHLYSDL
  SDALVIFQLYEKIKVPVDWNRVNKPPYPKLGGNMKKLENCNYAVELGKNQAKFSLVGIGG
  QDLNEGNRTLTLALIWQLMRRYTLNILEEIGGGQKVNDDIIVNWVNETLREAKKSSSISS
  FKDPKISTSLPVLDLIDAIQPGSINYDLLKTENLNDDEKLNNAKYAISMARKIGARVYAL
  PEDLVEVNPKMVMTVFACLMGKGMKRV
• Function: Actin-binding protein. Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28. Modulates the cell surface expression of IL2RA/CD25 and CD69.
• Tissue Specificity: Detected in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia, in spleen and other lymph node-containing organs. Expressed in peripheral blood T-lymphocytes, neutrophils, monocytes, B-lymphocytes, and myeloid cells.
• Reactome Pathway: Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Prostate cancer	DISF190Y	Definitive	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Definitive	Genetic Variation	[3]
Coloboma	DISP39N5	Strong	Genetic Variation	[4]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[8]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[9]
Melanoma	DIS1RRCY	Strong	Altered Expression	[10]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[11]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[8]
Nicotine dependence	DISZD9W7	Strong	Biomarker	[12]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[13]
Oral cancer	DISLD42D	Strong	Biomarker	[14]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[7]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[15]
Sarcoma	DISZDG3U	Strong	Biomarker	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[11]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[18]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Plastin-2 (LCP1) affects the response to substance of Nicotine.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Plastin-2 (LCP1).	[19]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Plastin-2 (LCP1).	[24]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Plastin-2 (LCP1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Plastin-2 (LCP1).	[40]
Calyculin-A	DMY29Q8	Investigative	Calyculin-A increases the phosphorylation of Plastin-2 (LCP1).	[35]

21 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 Plastin-2 (LCP1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Plastin-2 (LCP1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Plastin-2 (LCP1).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Plastin-2 (LCP1).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Plastin-2 (LCP1).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Plastin-2 (LCP1).	[26]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Plastin-2 (LCP1).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Plastin-2 (LCP1).	[28]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Plastin-2 (LCP1).	[29]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Plastin-2 (LCP1).	[30]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Plastin-2 (LCP1).	[31]
Hydroxyflutamide	DMGIZF5	Approved	Hydroxyflutamide decreases the expression of Plastin-2 (LCP1).	[32]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Plastin-2 (LCP1).	[33]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Plastin-2 (LCP1).	[34]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Plastin-2 (LCP1).	[36]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Plastin-2 (LCP1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Plastin-2 (LCP1).	[38]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Plastin-2 (LCP1).	[39]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Plastin-2 (LCP1).	[37]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Plastin-2 (LCP1).	[41]
1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane	DMDJYHK	Investigative	1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane increases the expression of Plastin-2 (LCP1).	[34]

References

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• [28] 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.
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• [32] Androgen receptor modulation following combination exposure to brominated flame-retardants. Sci Rep. 2018 Mar 19;8(1):4843. doi: 10.1038/s41598-018-23181-0.
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• [35] Possible involvement of optimally phosphorylated L-plastin in activation of superoxide-generating NADPH oxidase. J Biochem. 2003 Dec;134(6):827-34. doi: 10.1093/jb/mvg208.
• [36] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
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• [40] 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.
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