Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA246TE)

• DOT Name: Alpha-globin transcription factor CP2 (TFCP2)
• Synonyms: SAA3 enhancer factor; Transcription factor LSF
• Gene Name: TFCP2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Acute erythroid leukemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Epilepsy
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Major depressive disorder
  Neoplasm
  Pancreatic cancer
  Metastatic sarcoma
  Rhabdomyosarcoma
  Alzheimer disease
  Melanoma
• UniProt ID: TFCP2_HUMAN
• Pfam ID: PF04516 ; PF18016
• Sequence:
  MAWALKLPLADEVIESGLVQDFDASLSGIGQELGAGAYSMSDVLALPIFKQEESSLPPDN
  ENKILPFQYVLCAATSPAVKLHDETLTYLNQGQSYEIRMLDNRKLGELPEINGKLVKSIF
  RVVFHDRRLQYTEHQQLEGWRWNRPGDRILDIDIPMSVGIIDPRANPTQLNTVEFLWDPA
  KRTSVFIQVHCISTEFTMRKHGGEKGVPFRVQIDTFKENENGEYTEHLHSASCQIKVFKP
  KGADRKQKTDREKMEKRTPHEKEKYQPSYETTILTECSPWPEITYVNNSPSPGFNSSHSS
  FSLGEGNGSPNHQPEPPPPVTDNLLPTTTPQEAQQWLHRNRFSTFTRLFTNFSGADLLKL
  TRDDVIQICGPADGIRLFNALKGRMVRPRLTIYVCQESLQLREQQQQQQQQQQKHEDGDS
  NGTFFVYHAIYLEELTAVELTEKIAQLFSISPCQISQIYKQGPTGIHVLISDEMIQNFQE
  EACFILDTMKAETNDSYHIILK
• Function: Binds a variety of cellular and viral promoters including fibrinogen, alpha-globin, SV40 and HIV-1 promoters. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with UBP1. Functions as part of the SSP (stage selector protein) complex. Facilitates the interaction of the gamma-globin genes with enhancer elements contained in the locus control region in fetal erythroid cells. Interacts by binding to the stage selector element (SSE) in the proximal gamma-globin promoter.
• Tissue Specificity: Ubiquitous. Expressed in brain, ovary, kidney, thymus, spleen, liver, adrenal, heart and lung (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Epilepsy	DISBB28L	Strong	Altered Expression	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
leukaemia	DISS7D1V	Strong	Altered Expression	[8]
Leukemia	DISNAKFL	Strong	Altered Expression	[8]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[10]
Metastatic sarcoma	DISKYC7V	moderate	Biomarker	[11]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[12]
Alzheimer disease	DISF8S70	Limited	Biomarker	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Alpha-globin transcription factor CP2 (TFCP2).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[19]
Isoflavone	DM7U58J	Phase 4	Isoflavone affects the expression of Alpha-globin transcription factor CP2 (TFCP2).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[21]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Alpha-globin transcription factor CP2 (TFCP2).	[22]

References

• [1] CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer.Cell Death Dis. 2019 Sep 9;10(9):644. doi: 10.1038/s41419-019-1894-5.
• [2] Hemoglobin switching in man and chicken is mediated by a heteromeric complex between the ubiquitous transcription factor CP2 and a developmentally specific protein.EMBO J. 1995 Jan 3;14(1):97-105. doi: 10.1002/j.1460-2075.1995.tb06979.x.
• [3] A lymph node metastasis-related protein-coding genes combining with long noncoding RNA signature for breast cancer survival prediction.J Cell Physiol. 2019 Nov;234(11):20036-20045. doi: 10.1002/jcp.28600. Epub 2019 Apr 4.
• [4] TFCP2/TFCP2L1/UBP1 transcription factors in cancer.Cancer Lett. 2018 Apr 28;420:72-79. doi: 10.1016/j.canlet.2018.01.078. Epub 2018 Feb 7.
• [5] Glucose Deficiency Elevates Acid-Sensing Ion Channel 2a Expression and Increases Seizure Susceptibility in Temporal Lobe Epilepsy.Sci Rep. 2017 Jul 19;7(1):5870. doi: 10.1038/s41598-017-05038-0.
• [6] Expression and prognostic significance of MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) in ESCC tissues.Pathol Res Pract. 2019 Jul;215(7):152446. doi: 10.1016/j.prp.2019.152446. Epub 2019 May 8.
• [7] Same-Day Yttrium-90 Radioembolization: Feasibility with Resin Microspheres.J Vasc Interv Radiol. 2019 Mar;30(3):314-319. doi: 10.1016/j.jvir.2018.10.016.
• [8] Identification and characterization of a soluble suppressor factor(s) in the serum of AKR mice bearing lymphocytic leukemia.Cell Immunol. 1983 Nov;82(1):163-73. doi: 10.1016/0008-8749(83)90150-8.
• [9] Association of polymorphism in the transcription factor LBP-1c/CP2/LSF gene with Alzheimer's disease and major depression.Dement Geriatr Cogn Disord. 2006;22(1):95-8. doi: 10.1159/000093460. Epub 2006 May 18.
• [10] TFCP2 activates beta-catenin/TCF signaling in the progression of pancreatic cancer.Oncotarget. 2017 Jul 31;8(41):70538-70549. doi: 10.18632/oncotarget.19741. eCollection 2017 Sep 19.
• [11] Spindle cell rhabdomyosarcoma in a lumbar vertebra with FUS-TFCP2 fusion.Pathol Res Pract. 2019 Aug;215(8):152399. doi: 10.1016/j.prp.2019.03.027. Epub 2019 Mar 27.
• [12] A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation.Mod Pathol. 2020 Mar;33(3):404-419. doi: 10.1038/s41379-019-0323-8. Epub 2019 Aug 5.
• [13] A pectin from fruits of Lycium barbarum L. decreases -amyloid peptide production through modulating APP processing.Carbohydr Polym. 2018 Dec 1;201:65-74. doi: 10.1016/j.carbpol.2018.08.050. Epub 2018 Aug 15.
• [14] Transcription factor LSF (TFCP2) inhibits melanoma growth.Oncotarget. 2016 Jan 19;7(3):2379-90. doi: 10.18632/oncotarget.6230.
• [15] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [16] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [19] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [20] Soy isoflavones alter expression of genes associated with cancer progression, including interleukin-8, in androgen-independent PC-3 human prostate cancer cells. J Nutr. 2006 Jan;136(1):75-82.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.