Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB73XXA)

DOT Name	Pleckstrin (PLEK)
Synonyms	Platelet 47 kDa protein; p47
Gene Name	PLEK
Related Disease	Episodic kinesigenic dyskinesia 1 ( ) Aarskog-Scott syndrome, X-linked ( ) Adult glioblastoma ( ) Adult T-cell leukemia/lymphoma ( ) Advanced cancer ( ) Age-related macular degeneration ( ) Alzheimer disease ( ) Bruton-type agammaglobulinemia ( ) Centronuclear myopathy ( ) Charcot marie tooth disease ( ) Chronic granulomatous disease ( ) Coeliac disease ( ) Endometrial carcinoma ( ) Esophageal squamous cell carcinoma ( ) Familial adenomatous polyposis ( ) Glioma ( ) Human T-lymphotropic virus 1 infectious disease ( ) Hyperlipidemia ( ) Immunodeficiency ( ) Leukemia ( ) Lung cancer ( ) Multiple sclerosis ( ) Obstructive sleep apnea ( ) Osteoporosis ( ) Pancreatic cancer ( ) Rheumatoid arthritis ( ) Thrombocytopenia ( ) Transitional cell carcinoma ( ) Urothelial carcinoma ( ) Vascular dementia ( ) Venous thromboembolism ( ) Vibrio cholerae infection ( ) Asthma ( ) Autoimmune disease ( ) Breast cancer ( ) Breast carcinoma ( ) Hirschsprung disease ( ) Immune system disorder ( ) Melanoma ( ) Periodontitis ( ) Glioblastoma multiforme ( ) Malaria ( ) Neoplasm ( ) Non-insulin dependent diabetes ( ) Obesity ( ) Parkinson disease ( ) T-cell leukaemia ( ) Type-1 diabetes ( ) Type-1/2 diabetes ( )
UniProt ID	PLEK_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1PLS; 1W4M; 1X05; 1XX0; 1ZM0; 2CSO; 2I5C; 2I5F
Pfam ID	PF00610 ; PF00169
Sequence	MEPKRIREGYLVKKGSVFNTWKPMWVVLLEDGIEFYKKKSDNSPKGMIPLKGSTLTSPCQ DFGKRMFVFKITTTKQQDHFFQAAFLEERDAWVRDIKKAIKCIEGGQKFARKSTRRSIRL PETIDLGALYLSMKDTEKGIKELNLEKDKKIFNHCFTGNCVIDWLVSNQSVRNRQEGLMI ASSLLNEGYLQPAGDMSKSAVDGTAENPFLDNPDAFYYFPDSGFFCEENSSDDDVILKEE FRGVIIKQGCLLKQGHRRKNWKVRKFILREDPAYLHYYDPAGAEDPLGAIHLRGCVVTSV ESNSNGRKSEEENLFEIITADEVHYFLQAATPKERTEWIRAIQMASRTGK
Function	Major protein kinase C substrate of platelets.
Reactome Pathway	Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Episodic kinesigenic dyskinesia 1	DISGVQMP	Definitive	Biomarker	[1]
Aarskog-Scott syndrome, X-linked	DISNHV62	Strong	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Genetic Variation	[8]
Centronuclear myopathy	DISXBEJO	Strong	Genetic Variation	[9]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[10]
Chronic granulomatous disease	DIS9ZR24	Strong	Genetic Variation	[11]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[12]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[14]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Biomarker	[16]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	Strong	Biomarker	[4]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[17]
Immunodeficiency	DIS093I0	Strong	Biomarker	[18]
Leukemia	DISNAKFL	Strong	Genetic Variation	[19]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[20]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[21]
Obstructive sleep apnea	DIS0SVD1	Strong	Genetic Variation	[22]
Osteoporosis	DISF2JE0	Strong	Biomarker	[23]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Thrombocytopenia	DISU61YW	Strong	Biomarker	[26]
Transitional cell carcinoma	DISWVVDR	Strong	Genetic Variation	[27]
Urothelial carcinoma	DISRTNTN	Strong	Genetic Variation	[27]
Vascular dementia	DISVO82H	Strong	Biomarker	[28]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[29]
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[30]
Asthma	DISW9QNS	moderate	Altered Expression	[31]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[32]
Breast cancer	DIS7DPX1	moderate	Biomarker	[33]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[33]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[34]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[32]
Melanoma	DIS1RRCY	moderate	Posttranslational Modification	[35]
Periodontitis	DISI9JOI	moderate	Altered Expression	[36]
Glioblastoma multiforme	DISK8246	Disputed	Genetic Variation	[3]
Malaria	DISQ9Y50	Limited	Biomarker	[37]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[38]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[39]
Obesity	DIS47Y1K	Limited	Biomarker	[39]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[40]
T-cell leukaemia	DISJ6YIF	Limited	Biomarker	[41]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[42]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[43]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pleckstrin (PLEK).	[44]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pleckstrin (PLEK).	[45]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pleckstrin (PLEK).	[46]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pleckstrin (PLEK).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Pleckstrin (PLEK).	[48]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Pleckstrin (PLEK).	[49]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Pleckstrin (PLEK).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pleckstrin (PLEK).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pleckstrin (PLEK).	[52]
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⏷ Show the Full List of 9 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Pleckstrin (PLEK).	[50]
5'-Guanosine-Diphosphate-Monothiophosphate	DMIARG7	Investigative	5'-Guanosine-Diphosphate-Monothiophosphate increases the phosphorylation of Pleckstrin (PLEK).	[50]
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References

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24	AKT1 (E17K) mutation in pancreatic cancer.Technol Cancer Res Treat. 2008 Oct;7(5):407-8. doi: 10.1177/153303460800700509.
25	From transcriptome to proteome: differentially expressed proteins identified in synovial tissue of patients suffering from rheumatoid arthritis and osteoarthritis by an initial screen with a panel of 791 antibodies.Proteomics. 2003 Jun;3(6):991-1002. doi: 10.1002/pmic.200300412.
26	Platelet protein kinase C-theta deficiency with human RUNX1 mutation: PRKCQ is a transcriptional target of RUNX1.Arterioscler Thromb Vasc Biol. 2011 Apr;31(4):921-7. doi: 10.1161/ATVBAHA.110.221879. Epub 2011 Jan 20.
27	AKT1 E17 K pleckstrin homology domain mutation in urothelial carcinoma.Cancer Genet Cytogenet. 2009 May;191(1):34-7. doi: 10.1016/j.cancergencyto.2009.01.009.
28	Functions of intronic nucleotide variants in the gene encoding pleckstrin homology like domain beta 2 (PHLDB2) on susceptibility to vascular dementia.World J Biol Psychiatry. 2013 Apr;14(3):227-32. doi: 10.3109/15622975.2011.630407. Epub 2011 Nov 23.
29	Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
30	A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.Am J Trop Med Hyg. 2017 Jul;97(1):30-37. doi: 10.4269/ajtmh.15-0771.
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32	Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
33	Novel inhibitors induce large conformational changes of GAB1 pleckstrin homology domain and kill breast cancer cells.PLoS Comput Biol. 2015 Jan 8;11(1):e1004021. doi: 10.1371/journal.pcbi.1004021. eCollection 2015 Jan.
34	Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease.Oncogene. 1998 Dec 10;17(23):3065-70. doi: 10.1038/sj.onc.1202226.
35	Oncogenic suppression of PHLPP1 in human melanoma.Oncogene. 2014 Sep 25;33(39):4756-66. doi: 10.1038/onc.2013.420. Epub 2013 Oct 14.
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37	Plasmodium P47: a key gene for malaria transmission by mosquito vectors.Curr Opin Microbiol. 2017 Dec;40:168-174. doi: 10.1016/j.mib.2017.11.029. Epub 2017 Dec 8.
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39	Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling.Diabetologia. 2011 Aug;54(8):2122-31. doi: 10.1007/s00125-011-2173-x. Epub 2011 May 12.
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