Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQDUCT6)

• DOT Name: Protein ECT2 (ECT2)
• Synonyms: Epithelial cell-transforming sequence 2 oncogene
• Gene Name: ECT2
• Related Disease:
  Adenocarcinoma
  Invasive breast carcinoma
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Advanced cancer
  Atrial fibrillation
  Bone osteosarcoma
  Breast carcinoma
  Clear cell renal carcinoma
  Convulsion
  Estrogen-receptor positive breast cancer
  Focal segmental glomerulosclerosis
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung squamous cell carcinoma
  Malignant glioma
  Obesity
  Oral cancer
  Osteosarcoma
  Pancreatic tumour
  Pituitary tumor
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Stomach cancer
  Triple negative breast cancer
  Astrocytoma
  Glioma
  Laryngeal squamous cell carcinoma
  Metastatic malignant neoplasm
  Adult glioblastoma
  Glioblastoma multiforme
  Breast cancer
  Colorectal carcinoma
  Inflammatory breast cancer
  Leukoplakia
  Non-small-cell lung cancer
  Pancreatic cancer
• UniProt ID: ECT2_HUMAN
• PDB ID: 3L46; 4N40; 6L30
• Pfam ID: PF00533 ; PF21243 ; PF21242 ; PF12738 ; PF00621
• Sequence:
  MAENSVLTSTTGRTSLADSSIFDSKVTEISKENLLIGSTSYVEEEMPQIETRVILVQEAG
  KQEELIKALKTIKIMEVPVIKIKESCPGKSDEKLIKSVINMDIKVGFVKMESVEEFEGLD
  SPEFENVFVVTDFQDSVFNDLYKADCRVIGPPVVLNCSQKGEPLPFSCRPLYCTSMMNLV
  LCFTGFRKKEELVRLVTLVHHMGGVIRKDFNSKVTHLVANCTQGEKFRVAVSLGTPIMKP
  EWIYKAWERRNEQDFYAAVDDFRNEFKVPPFQDCILSFLGFSDEEKTNMEEMTEMQGGKY
  LPLGDERCTHLVVEENIVKDLPFEPSKKLYVVKQEWFWGSIQMDARAGETMYLYEKANTP
  ELKKSVSMLSLNTPNSNRKRRRLKETLAQLSRETDVSPFPPRKRPSAEHSLSIGSLLDIS
  NTPESSINYGDTPKSCTKSSKSSTPVPSKQSARWQVAKELYQTESNYVNILATIIQLFQV
  PLEEEGQRGGPILAPEEIKTIFGSIPDIFDVHTKIKDDLEDLIVNWDESKSIGDIFLKYS
  KDLVKTYPPFVNFFEMSKETIIKCEKQKPRFHAFLKINQAKPECGRQSLVELLIRPVQRL
  PSVALLLNDLKKHTADENPDKSTLEKAIGSLKEVMTHINEDKRKTEAQKQIFDVVYEVDG
  CPANLLSSHRSLVQRVETISLGEHPCDRGEQVTLFLFNDCLEIARKRHKVIGTFRSPHGQ
  TRPPASLKHIHLMPLSQIKKVLDIRETEDCHNAFALLVRPPTEQANVLLSFQMTSDELPK
  ENWLKMLCRHVANTICKADAENLIYTADPESFEVNTKDMDSTLSRASRAIKKTSKKVTRA
  FSFSKTPKRALRRALMTSHGSVEGRSPSSNDKHVMSRLSSTSSLAGIPSPSLVSLPSFFE
  RRSHTLSRSTTHLI
• Function: Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.
• Tissue Specificity: Expressed in lung epithelial cells (at protein level). Expressed in squamous cell carcinoma, primary non-small cell lung cancer tumors and lung adenocarcinoma.
• Reactome Pathway:
  G alpha (12/13) signalling events (R-HSA-416482)
  RHOA GTPase cycle (R-HSA-8980692)
  RHOB GTPase cycle (R-HSA-9013026)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  NRAGE signals death through JNK (R-HSA-193648)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Invasive breast carcinoma	DISANYTW	Definitive	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[3]
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Convulsion	DIS1CYA2	Strong	Biomarker	[10]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[11]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Genetic Variation	[12]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[13]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Lung squamous cell carcinoma	DISXPIBD	Strong	Genetic Variation	[16]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[17]
Obesity	DIS47Y1K	Strong	Biomarker	[18]
Oral cancer	DISLD42D	Strong	Altered Expression	[19]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Pancreatic tumour	DIS3U0LK	Strong	Posttranslational Modification	[20]
Pituitary tumor	DISN67JD	Strong	Biomarker	[21]
Prostate cancer	DISF190Y	Strong	Altered Expression	[22]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[22]
Pulmonary fibrosis	DISQKVLA	Strong	Altered Expression	[23]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[13]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[24]
Astrocytoma	DISL3V18	moderate	Biomarker	[25]
Glioma	DIS5RPEH	moderate	Altered Expression	[21]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[26]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[27]
Adult glioblastoma	DISVP4LU	Disputed	Altered Expression	[28]
Glioblastoma multiforme	DISK8246	Disputed	Altered Expression	[28]
Breast cancer	DIS7DPX1	Limited	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[29]
Inflammatory breast cancer	DIS3QRWA	Limited	Biomarker	[8]
Leukoplakia	DIST3QD3	Limited	Genetic Variation	[30]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[31]
Pancreatic cancer	DISJC981	Limited	Biomarker	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein ECT2 (ECT2).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein ECT2 (ECT2).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein ECT2 (ECT2).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein ECT2 (ECT2).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein ECT2 (ECT2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein ECT2 (ECT2).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein ECT2 (ECT2).	[39]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein ECT2 (ECT2).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein ECT2 (ECT2).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein ECT2 (ECT2).	[42]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein ECT2 (ECT2).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein ECT2 (ECT2).	[43]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Protein ECT2 (ECT2).	[44]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein ECT2 (ECT2).	[45]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Protein ECT2 (ECT2).	[46]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Protein ECT2 (ECT2).	[47]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Protein ECT2 (ECT2).	[48]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein ECT2 (ECT2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein ECT2 (ECT2).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein ECT2 (ECT2).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein ECT2 (ECT2).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein ECT2 (ECT2).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein ECT2 (ECT2).	[54]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Protein ECT2 (ECT2).	[55]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein ECT2 (ECT2).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein ECT2 (ECT2).	[50]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein ECT2 (ECT2).	[52]

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