Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPP742Z)

• DOT Name: G2 and S phase-expressed protein 1 (GTSE1)
• Synonyms: GTSE-1; Protein B99 homolog
• Gene Name: GTSE1
• Related Disease:
  Melanoma
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Pulmonary fibrosis
  Stomach cancer
  Triple negative breast cancer
  Advanced cancer
  Hepatocellular carcinoma
  Adenocarcinoma
  Bladder cancer
  Lung carcinoma
  Neoplasm
  Neuroblastoma
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: GTSE1_HUMAN
• PDB ID: 6QNN; 6QNP
• Pfam ID: PF15259
• Sequence:
  MEGGGGRDEPSACRAGDVNMDDPKKEDILLLADEKFDFDLSLSSSSANEDDEVFFGPFGH
  KERCIAASLELNNPVPEQPPLPTSESPFAWSPLAGEKFVEVYKEAHLLALHIESSSRNQA
  AQAAKPEDPRSQGVERFIQESKLKINLFEKEKEMKKSPTSLKRETYYLSDSPLLGPPVGE
  PRLLASSPALPSSGAQARLTRAPGPPHSAHALPRESCTAHAASQAATQRKPGTKLLLPRA
  ASVRGRSIPGAAEKPKKEIPASPSRTKIPAEKESHRDVLPDKPAPGAVNVPAAGSHLGQG
  KRAIPVPNKLGLKKTLLKAPGSTSNLARKSSSGPVWSGASSACTSPAVGKAKSSEFASIP
  ANSSRPLSNISKSGRMGPAMLRPALPAGPVGASSWQAKRVDVSELAAEQLTAPPSASPTQ
  PQTPEGGGQWLNSSCAWSESSQLNKTRSIRRRDSCLNSKTKVMPTPTNQFKIPKFSIGDS
  PDSSTPKLSRAQRPQSCTSVGRVTVHSTPVRRSSGPAPQSLLSAWRVSALPTPASRRCSG
  LPPMTPKTMPRAVGSPLCVPARRRSSEPRKNSAMRTEPTRESNRKTDSRLVDVSPDRGSP
  PSRVPQALNFSPEESDSTFSKSTATEVAREEAKPGGDAAPSEALLVDIKLEPLAVTPDAA
  SQPLIDLPLIDFCDTPEAHVAVGSESRPLIDLMTNTPDMNKNVAKPSPVVGQLIDLSSPL
  IQLSPEADKENVDSPLLKF
• Function: May be involved in p53-induced cell cycle arrest in G2/M phase by interfering with microtubule rearrangements that are required to enter mitosis. Overexpression delays G2/M phase progression.
• KEGG Pathway: p53 sig.ling pathway (hsa04115)
• Reactome Pathway:
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  G2/M Checkpoints (R-HSA-69481)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[3]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[3]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[6]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[7]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[8]
Lung carcinoma	DISTR26C	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Altered Expression	[9]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[9]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[7]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[8]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	G2 and S phase-expressed protein 1 (GTSE1) affects the response to substance of Vinblastine.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of G2 and S phase-expressed protein 1 (GTSE1).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[18]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[18]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[19]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[25]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[21]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of G2 and S phase-expressed protein 1 (GTSE1).	[27]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[29]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of G2 and S phase-expressed protein 1 (GTSE1).	[36]

4 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 G2 and S phase-expressed protein 1 (GTSE1).	[31]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of G2 and S phase-expressed protein 1 (GTSE1).	[33]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of G2 and S phase-expressed protein 1 (GTSE1).	[33]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of G2 and S phase-expressed protein 1 (GTSE1).	[37]

References

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• [2] GTSE1 is involved in breast cancer progression in p53 mutation-dependent manner.J Exp Clin Cancer Res. 2019 Apr 8;38(1):152. doi: 10.1186/s13046-019-1157-4.
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