Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJL4348)

• DOT Name: Transcription factor-like 5 protein (TCFL5)
• Synonyms: Cha transcription factor; HPV-16 E2-binding protein 1; E2BP-1
• Gene Name: TCFL5
• Related Disease:
  Acute lymphocytic leukaemia
  Adenoma
  Adult glioblastoma
  Cardiac failure
  Childhood acute lymphoblastic leukemia
  Congestive heart failure
  Cystic fibrosis
  Endometrium adenocarcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Hyperinsulinemia
  Myocardial infarction
  Neoplasm
  Polycystic ovarian syndrome
  Seminoma
  Stroke
  Type-1/2 diabetes
  Bone development disease
  Female hypogonadism
  Peripheral arterial disease
  Advanced cancer
  Atrial fibrillation
• UniProt ID: TCFL5_HUMAN
• Pfam ID: PF00010
• Sequence:
  MSGPGPREPPPEAGAAGGEAAVEGAGGGDAALGEPGLSFTTTDLSLVEMTEVEYTQLQHI
  LCSHMEAAADGELETRLNSALLAAAGPGAGAGGFAAGGQGGAAPVYPVLCPSALAADAPC
  LGHIDFQELRMMLLSEAGAAEKTSGGGDGARARADGAAKEGAGAAAAAAGPDGAPEARAK
  PAVRVRLEDRFNSIPAEPPPAPRGPEPPEPGGALNNLVTLIRHPSELMNVPLQQQNKCTA
  LVKNKTAATTTALQFTYPLFTTNACSTSGNSNLSQTQSSSNSCSVLEAAKHQDIGLPRAF
  SFCYQQEIESTKQTLGSRNKVLPEQVWIKVGEAALCKQALKRNRSRMRQLDTNVERRALG
  EIQNVGEGATATQGAWQSSESSQANLGEQAQSGPQGGRSQRRERHNRMERDRRRRIRICC
  DELNLLVPFCNAETDKATTLQWTTAFLKYIQERHGDSLKKEFESVFCGKTGRRLKLTRPD
  SLVTCPAQGSLQSSPSMEIK
• Function: Putative transcription factor. Isoform 3 may play a role in early spermatogenesis.
• Tissue Specificity: Isoform 3 is testis specific. Isoform 2 is pancreas specific.

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[5]
Endometrium adenocarcinoma	DISY6744	Strong	Genetic Variation	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[9]
Myocardial infarction	DIS655KI	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[11]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[12]
Stroke	DISX6UHX	Strong	Biomarker	[13]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[14]
Bone development disease	DISVKAZS	moderate	Biomarker	[15]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[16]
Peripheral arterial disease	DIS78WFB	moderate	Genetic Variation	[17]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[18]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Transcription factor-like 5 protein (TCFL5) affects the response to substance of Etoposide.	[28]

7 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 Transcription factor-like 5 protein (TCFL5).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor-like 5 protein (TCFL5).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor-like 5 protein (TCFL5).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor-like 5 protein (TCFL5).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transcription factor-like 5 protein (TCFL5).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor-like 5 protein (TCFL5).	[25]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Transcription factor-like 5 protein (TCFL5).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transcription factor-like 5 protein (TCFL5).	[27]

References

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• [8] Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.World J Gastroenterol. 2015 Dec 14;21(46):13064-72. doi: 10.3748/wjg.v21.i46.13064.
• [9] Altitude Acclimatization Alleviates the Hypoxia-Induced Suppression of Exogenous Glucose Oxidation During Steady-State Aerobic Exercise.Front Physiol. 2018 Jul 9;9:830. doi: 10.3389/fphys.2018.00830. eCollection 2018.
• [10] Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location.Stroke. 2012 Aug;43(8):2036-41. doi: 10.1161/STROKEAHA.111.648725. Epub 2012 May 24.
• [11] Genetic variations of follicle stimulating hormone receptor are associated with polycystic ovary syndrome.Int J Mol Med. 2010 Jul;26(1):107-12. doi: 10.3892/ijmm_00000441.
• [12] Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene.Cancer Res. 2006 Jan 1;66(1):290-302. doi: 10.1158/0008-5472.CAN-05-2936.
• [13] Practical Considerations for the Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation.Clin Appl Thromb Hemost. 2017 Jan;23(1):5-19. doi: 10.1177/1076029616634886. Epub 2016 Mar 17.
• [14] Targeting the CDA1/CDA1BP1 Axis Retards Renal Fibrosis in Experimental Diabetic Nephropathy.Diabetes. 2019 Feb;68(2):395-408. doi: 10.2337/db18-0712. Epub 2018 Nov 13.
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• [16] Epistasis between IGF2R and ADAMTS19 polymorphisms associates with premature ovarian failure.Hum Reprod. 2013 Nov;28(11):3146-54. doi: 10.1093/humrep/det365. Epub 2013 Sep 7.
• [17] CHADS? CHADSASc, and New ABCD Scores Predict the Risk of Peripheral Arterial Disease in Patients with Sleep Apnea.J Clin Med. 2019 Feb 5;8(2):188. doi: 10.3390/jcm8020188.
• [18] Usefulness of Amplatzer Vascular Plug for Preoperative Embolization Before Distal Pancreatectomy with En Bloc Celiac Axis Resection.Cardiovasc Intervent Radiol. 2019 Sep;42(9):1352-1357. doi: 10.1007/s00270-019-02233-6. Epub 2019 May 10.
• [19] Clinical Implications of Preoperative Nonvalvular Atrial Fibrillation with Respect to Postoperative Cardiovascular Outcomes in Patients Undergoing Non-Cardiac Surgery.Korean Circ J. 2020 Feb;50(2):148-159. doi: 10.4070/kcj.2019.0219. Epub 2019 Nov 19.
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• [22] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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• [26] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [27] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [28] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.