Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJRG4ES)

• DOT Name: Src substrate cortactin (CTTN)
• Synonyms: Amplaxin; Oncogene EMS1
• Gene Name: CTTN
• Related Disease:
  Glioma
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Colorectal neoplasm
  Congestive heart failure
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Juvenile idiopathic arthritis
  Laryngeal carcinoma
  Laryngeal disorder
  Liver cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Oral cancer
  Osteosarcoma
  Small lymphocytic lymphoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Leukoplakia
  Melanoma
  Prostate cancer
  Carcinoma
  Asthma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Cutaneous squamous cell carcinoma
  Prostate carcinoma
• UniProt ID: SRC8_HUMAN
• PDB ID: 1X69; 2D1X
• Pfam ID: PF02218 ; PF14604
• Sequence:
  MWKASAGHAVSIAQDDAGADDWETDPDFVNDVSEKEQRWGAKTVQGSGHQEHINIHKLRE
  NVFQEHQTLKEKELETGPKASHGYGGKFGVEQDRMDKSAVGHEYQSKLSKHCSQVDSVRG
  FGGKFGVQMDRVDQSAVGFEYQGKTEKHASQKDYSSGFGGKYGVQADRVDKSAVGFDYQG
  KTEKHESQRDYSKGFGGKYGIDKDKVDKSAVGFEYQGKTEKHESQKDYVKGFGGKFGVQT
  DRQDKCALGWDHQEKLQLHESQKDYKTGFGGKFGVQSERQDSAAVGFDYKEKLAKHESQQ
  DYSKGFGGKYGVQKDRMDKNASTFEDVTQVSSAYQKTVPVEAVTSKTSNIRANFENLAKE
  KEQEDRRKAEAERAQRMAKERQEQEEARRKLEEQARAKTQTPPVSPAPQPTEERLPSSPV
  YEDAASFKAELSYRGPVSGTEPEPVYSMEAADYREASSQQGLAYATEAVYESAEAPGHYP
  AEDSTYDEYENDLGITAVALYDYQAAGDDEISFDPDDIITNIEMIDDGWWRGVCKGRYGL
  FPANYVELRQ
• Function: Contributes to the organization of the actin cytoskeleton and cell shape. Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones. Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density. Plays a role in focal adhesion assembly and turnover. In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane. Plays a role in receptor-mediated endocytosis via clathrin-coated pits. Required for stabilization of KCNH1 channels at the cell membrane. Plays a role in the invasiveness of cancer cells, and the formation of metastases.
• KEGG Pathway:
  Tight junction (hsa04530)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RHO GTPases activate PAKs (R-HSA-5627123)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[11]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[14]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[18]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[19]
Laryngeal carcinoma	DISNHCIV	Strong	Genetic Variation	[20]
Laryngeal disorder	DISDKUQO	Strong	Biomarker	[21]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[9]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[22]
Lung cancer	DISCM4YA	Strong	Biomarker	[23]
Lung carcinoma	DISTR26C	Strong	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[24]
Neoplasm	DISZKGEW	Strong	Biomarker	[25]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[23]
Oral cancer	DISLD42D	Strong	Biomarker	[25]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[26]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[15]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[27]
Leukoplakia	DIST3QD3	moderate	Altered Expression	[28]
Melanoma	DIS1RRCY	moderate	Biomarker	[29]
Prostate cancer	DISF190Y	moderate	Altered Expression	[30]
Carcinoma	DISH9F1N	Disputed	Altered Expression	[31]
Asthma	DISW9QNS	Limited	Biomarker	[32]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[33]
Colon cancer	DISVC52G	Limited	Altered Expression	[34]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[34]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[35]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[30]

6 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 Src substrate cortactin (CTTN).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Src substrate cortactin (CTTN).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Src substrate cortactin (CTTN).	[55]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Src substrate cortactin (CTTN).	[56]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Src substrate cortactin (CTTN).	[56]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Src substrate cortactin (CTTN).	[60]

25 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 Src substrate cortactin (CTTN).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Src substrate cortactin (CTTN).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Src substrate cortactin (CTTN).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Src substrate cortactin (CTTN).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Src substrate cortactin (CTTN).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Src substrate cortactin (CTTN).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Src substrate cortactin (CTTN).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Src substrate cortactin (CTTN).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Src substrate cortactin (CTTN).	[46]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Src substrate cortactin (CTTN).	[47]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Src substrate cortactin (CTTN).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Src substrate cortactin (CTTN).	[48]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Src substrate cortactin (CTTN).	[49]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Src substrate cortactin (CTTN).	[42]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Src substrate cortactin (CTTN).	[50]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Src substrate cortactin (CTTN).	[51]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Src substrate cortactin (CTTN).	[42]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Src substrate cortactin (CTTN).	[42]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Src substrate cortactin (CTTN).	[42]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Src substrate cortactin (CTTN).	[53]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Src substrate cortactin (CTTN).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Src substrate cortactin (CTTN).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Src substrate cortactin (CTTN).	[58]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Src substrate cortactin (CTTN).	[59]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Src substrate cortactin (CTTN).	[61]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin affects the localization of Src substrate cortactin (CTTN).	[52]

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