Details of Drug Off-Target (DOT)

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

• DOT Name: Histone RNA hairpin-binding protein (SLBP)
• Synonyms: Histone stem-loop-binding protein
• Gene Name: SLBP
• Related Disease:
  Lattice corneal dystrophy type I
  Non-insulin dependent diabetes
  Abscess
  Alzheimer disease
  Bacterial meningitis
  Bone osteosarcoma
  Breast cancer
  Chronic obstructive pulmonary disease
  Coloboma
  Congestive heart failure
  Diabetic kidney disease
  Fatty liver disease
  Intrahepatic cholangiocarcinoma
  Knee osteoarthritis
  Osteosarcoma
  Wolf-Hirschhorn syndrome
  Bacterial infection
  Hepatocellular carcinoma
  Prostate cancer
• UniProt ID: SLBP_HUMAN
• PDB ID: 2KJM; 4L8R; 4QOZ
• Pfam ID: PF15247
• Sequence:
  MACRPRSPPRHQSRCDGDASPPSPARWSLGRKRRADGRRWRPEDAEEAEHRGAERRPESF
  TTPEGPKPRSRCSDWASAVEEDEMRTRVNKEMARYKRKLLINDFGRERKSSSGSSDSKES
  MSTVPADFETDESVLMRRQKQINYGKNTIAYDRYIKEVPRHLRQPGIHPKTPNKFKKYSR
  RSWDQQIKLWKVALHFWDPPAEEGCDLQEIHPVDLESAESSSEPQTSSQDDFDVYSGTPT
  KVRHMDSQVEDEFDLEACLTEPLRDFSAMS
• Function: RNA-binding protein involved in the histone pre-mRNA processing. Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery. Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression. Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis. Binds to the 5' side of the stem-loop structure of histone pre-mRNAs.
• Tissue Specificity: Widely expressed.
• Reactome Pathway:
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs (R-HSA-77588)
  Transport of the SLBP Dependant Mature mRNA (R-HSA-159230)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lattice corneal dystrophy type I	DISNKVHC	Definitive	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Abscess	DISAP982	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Bacterial meningitis	DISRP9SL	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[8]
Coloboma	DISP39N5	Strong	Biomarker	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[10]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[11]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[12]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[13]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Wolf-Hirschhorn syndrome	DISE4WMQ	Strong	Biomarker	[14]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[16]
Prostate cancer	DISF190Y	moderate	Altered Expression	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Histone RNA hairpin-binding protein (SLBP).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone RNA hairpin-binding protein (SLBP).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone RNA hairpin-binding protein (SLBP).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[23]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Histone RNA hairpin-binding protein (SLBP).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[26]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[27]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[28]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histone RNA hairpin-binding protein (SLBP).	[29]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Histone RNA hairpin-binding protein (SLBP).	[31]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Histone RNA hairpin-binding protein (SLBP).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Histone RNA hairpin-binding protein (SLBP).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Histone RNA hairpin-binding protein (SLBP).	[30]

References

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• [2] Isolated high home systolic blood pressure in patients with type 2 diabetes is a prognostic factor for the development of diabetic nephropathy: KAMOGAWA-HBP study.Diabetes Res Clin Pract. 2019 Dec;158:107920. doi: 10.1016/j.diabres.2019.107920. Epub 2019 Nov 8.
• [3] Escherichia coli hemoglobin protease autotransporter contributes to synergistic abscess formation and heme-dependent growth of Bacteroides fragilis.Infect Immun. 2002 Jan;70(1):5-10. doi: 10.1128/IAI.70.1.5-10.2002.
• [4] The Healthy Brain Project: An Online Platform for the Recruitment, Assessment, and Monitoring of Middle-Aged Adults at Risk of Developing Alzheimer's Disease.J Alzheimers Dis. 2019;68(3):1211-1228. doi: 10.3233/JAD-181139.
• [5] Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis.Braz J Microbiol. 2018 Nov;49 Suppl 1(Suppl 1):213-219. doi: 10.1016/j.bjm.2018.05.007. Epub 2018 Aug 17.
• [6] Knocking down miR-384 promotes growth and metastasis of osteosarcoma MG63 cells by targeting SLBP.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1458-1465. doi: 10.1080/21691401.2019.1601099.
• [7] Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer.Cell Death Dis. 2019 Oct 23;10(11):803. doi: 10.1038/s41419-019-2034-y.
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• [10] Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.J Diabetes Investig. 2019 Nov;10(6):1543-1549. doi: 10.1111/jdi.13040. Epub 2019 May 7.
• [11] Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.Eur Radiol. 2019 Jul;29(7):3791-3801. doi: 10.1007/s00330-019-06150-7. Epub 2019 Apr 1.
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• [14] Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome.Hum Mol Genet. 2012 May 15;21(10):2181-93. doi: 10.1093/hmg/dds033. Epub 2012 Feb 10.
• [15] Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis.J Intern Med. 2017 Jun;281(6):562-574. doi: 10.1111/joim.12604. Epub 2017 Mar 28.
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• [17] O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells.Cancer Res. 2013 Aug 15;73(16):5277-87. doi: 10.1158/0008-5472.CAN-13-0549. Epub 2013 May 29.
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• [19] 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.
• [20] 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.
• [21] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [22] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [23] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [24] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [25] 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.
• [26] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [27] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [28] Downregulation of Stem-Loop Binding Protein by Nicotine via 7-Nicotinic Acetylcholine Receptor and Its Role in Nicotine-Induced Cell Transformation. Toxicol Sci. 2022 Sep 24;189(2):186-202. doi: 10.1093/toxsci/kfac080.
• [29] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [30] 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.
• [31] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [32] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.