Details of Drug Off-Target (DOT)

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

• DOT Name: Heterogeneous nuclear ribonucleoprotein F (HNRNPF)
• Synonyms: hnRNP F; Nucleolin-like protein mcs94-1
• Gene Name: HNRNPF
• Related Disease:
  Non-insulin dependent diabetes
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Glioma
  Multiple endocrine neoplasia type 2A
  Neoplasm
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal neoplasm
  High blood pressure
  Type-1 diabetes
• UniProt ID: HNRPF_HUMAN
• PDB ID: 2HGL; 2HGM; 2HGN; 2KFY; 2KG0; 2KG1; 3TFY
• Pfam ID: PF00076 ; PF08080
• Sequence:
  MMLGPEGGEGFVVKLRGLPWSCSVEDVQNFLSDCTIHDGAAGVHFIYTREGRQSGEAFVE
  LGSEDDVKMALKKDRESMGHRYIEVFKSHRTEMDWVLKHSGPNSADSANDGFVRLRGLPF
  GCTKEEIVQFFSGLEIVPNGITLPVDPEGKITGEAFVQFASQELAEKALGKHKERIGHRY
  IEVFKSSQEEVRSYSDPPLKFMSVQRPGPYDRPGTARRYIGIVKQAGLERMRPGAYSTGY
  GGYEEYSGLSDGYGFTTDLFGRDLSYCLSGMYDHRYGDSEFTVQSTTGHCVHMRGLPYKA
  TENDIYNFFSPLNPVRVHIEIGPDGRVTGEADVEFATHEEAVAAMSKDRANMQHRYIELF
  LNSTTGASNGAYSSQVMQGMGVSAAQATYSGLESQSVSGCYGAGYSGQNSMGGYD
• Function: Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state.
• Tissue Specificity: Expressed ubiquitously.
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  FGFR2 alternative splicing (R-HSA-6803529)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Multiple endocrine neoplasia type 2A	DIS7D3W2	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[7]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[7]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[7]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Colon cancer	DISVC52G	Limited	Biomarker	[8]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[8]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[8]
High blood pressure	DISY2OHH	Limited	Biomarker	[9]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Heterogeneous nuclear ribonucleoprotein F (HNRNPF) affects the binding of PEITC.	[23]
Sulforaphane	DMQY3L0	Investigative	Heterogeneous nuclear ribonucleoprotein F (HNRNPF) affects the binding of Sulforaphane.	[23]

4 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 Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[21]

9 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 Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[15]
Marinol	DM70IK5	Approved	Marinol increases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[16]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[17]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[17]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Heterogeneous nuclear ribonucleoprotein F (HNRNPF).	[22]

References

• [1] Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression and Attenuates Nephropathy Progression in Diabetic Mice.Diabetes. 2017 Jul;66(7):1964-1978. doi: 10.2337/db16-1588. Epub 2017 Apr 19.
• [2] HnRNP-F promotes cell proliferation by regulating TPX2 in bladder cancer.Am J Transl Res. 2019 Nov 15;11(11):7035-7048. eCollection 2019.
• [3] RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF.Genes Dev. 2017 Nov 15;31(22):2296-2309. doi: 10.1101/gad.305862.117. Epub 2017 Dec 21.
• [4] Proteomic screening and identification of microRNA-128 targets in glioma cells.Proteomics. 2015 Aug;15(15):2602-17. doi: 10.1002/pmic.201400128. Epub 2015 May 15.
• [5] Identification and characterization of a gene at D10S94 in the MEN2A region.Genomics. 1992 Jun;13(2):344-8. doi: 10.1016/0888-7543(92)90251-m.
• [6] HnRNP-F regulates EMT in bladder cancer by mediating the stabilization of Snail1 mRNA by binding to its 3' UTR.EBioMedicine. 2019 Jul;45:208-219. doi: 10.1016/j.ebiom.2019.06.017. Epub 2019 Jun 18.
• [7] Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.Int J Cancer. 2020 Jan 15;146(2):521-530. doi: 10.1002/ijc.32622. Epub 2019 Aug 28.
• [8] Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer.Cancer Res. 2006 Jan 15;66(2):763-9. doi: 10.1158/0008-5472.CAN-05-3771.
• [9] Tubular Deficiency of Heterogeneous Nuclear Ribonucleoprotein F Elevates Systolic Blood Pressure and Induces Glycosuria in Mice.Sci Rep. 2019 Oct 31;9(1):15765. doi: 10.1038/s41598-019-52323-1.
• [10] Insulin Inhibits Nrf2 Gene Expression via Heterogeneous Nuclear Ribonucleoprotein F/K in Diabetic Mice.Endocrinology. 2017 Apr 1;158(4):903-919. doi: 10.1210/en.2016-1576.
• [11] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [12] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [13] 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.
• [14] 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.
• [15] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [16] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [17] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [18] Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
• [19] 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.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [23] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.