Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA6Q5E0)

• DOT Name: Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL)
• Synonyms: hnRNPLL; Stromal RNA-regulating factor
• Gene Name: HNRNPLL
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
• UniProt ID: HNRLL_HUMAN
• PDB ID: 7EVS
• Pfam ID: PF00076 ; PF13893 ; PF11835
• Sequence:
  MSSSSSSPRETYEEDREYESQAKRLKTEEGEIDYSAEEGENRREATPRGGGDGGGGGRSF
  SQPEAGGSHHKVSVSPVVHVRGLCESVVEADLVEALEKFGTICYVMMMPFKRQALVEFEN
  IDSAKECVTFAADEPVYIAGQQAFFNYSTSKRITRPGNTDDPSGGNKVLLLSIQNPLYPI
  TVDVLYTVCNPVGKVQRIVIFKRNGIQAMVEFESVLCAQKAKAALNGADIYAGCCTLKIE
  YARPTRLNVIRNDNDSWDYTKPYLGRRDRGKGRQRQAILGEHPSSFRHDGYGSHGPLLPL
  PSRYRMGSRDTPELVAYPLPQASSSYMHGGNPSGSVVMVSGLHQLKMNCSRVFNLFCLYG
  NIEKVKFMKTIPGTALVEMGDEYAVERAVTHLNNVKLFGKRLNVCVSKQHSVVPSQIFEL
  EDGTSSYKDFAMSKNNRFTSAGQASKNIIQPPSCVLHYYNVPLCVTEETFTKLCNDHEVL
  TFIKYKVFDAKPSAKTLSGLLEWECKTDAVEALTALNHYQIRVPNGSNPYTLKLCFSTSS
  HL
• Function: RNA-binding protein that functions as a regulator of alternative splicing for multiple target mRNAs, including PTPRC/CD45 and STAT5A. Required for alternative splicing of PTPRC.
• Tissue Specificity: Widely expressed. Detected in bone marrow stroma cells, skeletal muscle, heart, placenta, pancreas, kidney and lung.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[1]

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 L-like (HNRNPLL).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL).	[9]

References

• [1] HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition.Gut. 2018 Jun;67(6):1103-1111. doi: 10.1136/gutjnl-2016-312927. Epub 2017 Mar 30.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] 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.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.