Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJP4U7K)

• DOT Name: Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1)
• Synonyms: Adenovirus early region 1B-associated protein 5; E1B-55 kDa-associated protein 5; E1B-AP5
• Gene Name: HNRNPUL1
• Related Disease:
  Myocardial infarction
  Clear cell renal carcinoma
  Renal cell carcinoma
  Systemic lupus erythematosus
  Adenovirus infection
  Coronary heart disease
• UniProt ID: HNRL1_HUMAN
• Pfam ID: PF13671 ; PF02037 ; PF00622
• Sequence:
  MDVRRLKVNELREELQRRGLDTRGLKAELAERLQAALEAEEPDDERELDADDEPGRPGHI
  NEEVETEGGSELEGTAQPPPPGLQPHAEPGGYSGPDGHYAMDNITRQNQFYDTQVIKQEN
  ESGYERRPLEMEQQQAYRPEMKTEMKQGAPTSFLPPEASQLKPDRQQFQSRKRPYEENRG
  RGYFEHREDRRGRSPQPPAEEDEDDFDDTLVAIDTYNCDLHFKVARDRSSGYPLTIEGFA
  YLWSGARASYGVRRGRVCFEMKINEEISVKHLPSTEPDPHVVRIGWSLDSCSTQLGEEPF
  SYGYGGTGKKSTNSRFENYGDKFAENDVIGCFADFECGNDVELSFTKNGKWMGIAFRIQK
  EALGGQALYPHVLVKNCAVEFNFGQRAEPYCSVLPGFTFIQHLPLSERIRGTVGPKSKAE
  CEILMMVGLPAAGKTTWAIKHAASNPSKKYNILGTNAIMDKMRVMGLRRQRNYAGRWDVL
  IQQATQCLNRLIQIAARKKRNYILDQTNVYGSAQRRKMRPFEGFQRKAIVICPTDEDLKD
  RTIKRTDEEGKDVPDHAVLEMKANFTLPDVGDFLDEVLFIELQREEADKLVRQYNEEGRK
  AGPPPEKRFDNRGGGGFRGRGGGGGFQRYENRGPPGGNRGGFQNRGGGSGGGGNYRGGFN
  RSGGGGYSQNRWGNNNRDNNNSNNRGSYNRAPQQQPPPQQPPPPQPPPQQPPPPPSYSPA
  RNPPGASTYNKNSNIPGSSANTSTPTVSSYSPPQPSYSQPPYNQGGYSQGYTAPPPPPPP
  PPAYNYGSYGGYNPAPYTPPPPPTAQTYPQPSYNQYQQYAQQWNQYYQNQGQWPPYYGNY
  DYGSYSGNTQGGTSTQ
• Function: Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro.
• KEGG Pathway: Influenza A (hsa05164)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[3]
Adenovirus infection	DISUYSBZ	moderate	Altered Expression	[4]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[5]

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 Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[10]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[11]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[12]

4 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 decreases the methylation of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Heterogeneous nuclear ribonucleoprotein U-like protein 1 (HNRNPUL1).	[16]

References

• [1] Gene variants of VAMP8 and HNRPUL1 are associated with early-onset myocardial infarction.Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1613-8. doi: 10.1161/01.ATV.0000226543.77214.e4. Epub 2006 May 11.
• [2] Heterogeneous nuclear ribonucleoprotein U-like 1 and Poly (ADP-ribose) polymerase 1 are downregulated in renal cell carcinoma and connected with the prognosis.Cancer Biomark. 2013 Jan 1;13(6):411-5. doi: 10.3233/CBM-140390.
• [3] Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.Mol Immunol. 2006 Mar;43(9):1497-507. doi: 10.1016/j.molimm.2005.07.039. Epub 2005 Sep 6.
• [4] A role for E1B-AP5 in ATR signaling pathways during adenovirus infection.J Virol. 2008 Aug;82(15):7640-52. doi: 10.1128/JVI.00170-08. Epub 2008 May 14.
• [5] Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people.Genet Mol Res. 2014 Apr 8;13(2):2619-27. doi: 10.4238/2014.April.8.4.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] 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.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [12] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [13] 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.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] 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.