Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIMYS4W)

• DOT Name: Securin (PTTG1)
• Synonyms: Esp1-associated protein; Pituitary tumor-transforming gene 1 protein; Tumor-transforming protein 1; hPTTG
• Gene Name: PTTG1
• Related Disease:
  Advanced cancer
  Melanoma
  Meningioma
  Neoplasm of esophagus
  Adenoma
  Adrenocortical carcinoma
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Invasive ductal breast carcinoma
  Medullary thyroid gland carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Palmoplantar pustulosis
  Pancreatic cancer
  Pituitary tumor
  Psoriasis
  Sjogren syndrome
  Squamous cell carcinoma
  Stomach cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Type-1/2 diabetes
  Uterine fibroids
  Carcinoma
  Clear cell renal carcinoma
  Lung cancer
  Lung carcinoma
  Myeloid leukaemia
  Prostate cancer
  Prostate carcinoma
  Thyroid tumor
• UniProt ID: PTTG1_HUMAN
• PDB ID: 7NJ0; 7NJ1
• Pfam ID: PF04856
• Sequence:
  MATLIYVDKENGEPGTRVVAKDGLKLGSGPSIKALDGRSQVSTPRFGKTFDAPPALPKAT
  RKALGTVNRATEKSVKTKGPLKQKQPSFSAKKMTEKTVKAKSSVPASDDAYPEIEKFFPF
  NPLDFESFDLPEEHQIAHLPLSGVPLMILDEERELEKLFQLGPPSPVKMPSPPWESNLLQ
  SPSSILSTLDVELPPVCCDIDI
• Function: Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation.
• Tissue Specificity: Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  APC/C (R-HSA-174178)
  Separation of Sister Chromatids (R-HSA-2467813)
  APC/C (R-HSA-174154)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Meningioma	DISPT4TG	Definitive	Biomarker	[3]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[4]
Adenoma	DIS78ZEV	Strong	Altered Expression	[5]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[15]
Gastric cancer	DISXGOUK	Strong	Biomarker	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[19]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Altered Expression	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[14]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[14]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[22]
Pancreatic cancer	DISJC981	Strong	Posttranslational Modification	[23]
Pituitary tumor	DISN67JD	Strong	Biomarker	[1]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[24]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[16]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[27]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[28]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[29]
Carcinoma	DISH9F1N	moderate	Biomarker	[30]
Clear cell renal carcinoma	DISBXRFJ	moderate	Biomarker	[1]
Lung cancer	DISCM4YA	moderate	Biomarker	[31]
Lung carcinoma	DISTR26C	moderate	Biomarker	[31]
Myeloid leukaemia	DISMN944	Limited	Biomarker	[32]
Prostate cancer	DISF190Y	Limited	Altered Expression	[33]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[33]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[27]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Securin (PTTG1) affects the response to substance of Vinblastine.	[65]
Gefitinib	DM15F0X	Approved	Securin (PTTG1) decreases the response to substance of Gefitinib.	[66]

2 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 Securin (PTTG1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Securin (PTTG1).	[59]

34 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 Securin (PTTG1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Securin (PTTG1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Securin (PTTG1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Securin (PTTG1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Securin (PTTG1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Securin (PTTG1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Securin (PTTG1).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Securin (PTTG1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Securin (PTTG1).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Securin (PTTG1).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Securin (PTTG1).	[44]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Securin (PTTG1).	[45]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Securin (PTTG1).	[38]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Securin (PTTG1).	[41]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Securin (PTTG1).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Securin (PTTG1).	[47]
Paclitaxel	DMLB81S	Approved	Paclitaxel affects the expression of Securin (PTTG1).	[48]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Securin (PTTG1).	[49]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Securin (PTTG1).	[50]
LY2835219	DM93VBZ	Approved	LY2835219 decreases the expression of Securin (PTTG1).	[51]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Securin (PTTG1).	[52]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Securin (PTTG1).	[53]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Securin (PTTG1).	[54]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Securin (PTTG1).	[55]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Securin (PTTG1).	[56]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Securin (PTTG1).	[57]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Securin (PTTG1).	[58]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Securin (PTTG1).	[60]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Securin (PTTG1).	[53]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Securin (PTTG1).	[61]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Securin (PTTG1).	[43]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Securin (PTTG1).	[62]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Securin (PTTG1).	[63]
BUTEIN	DM8E54P	Investigative	BUTEIN decreases the expression of Securin (PTTG1).	[13]

References

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