Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIXO0Z4)

• DOT Name: Ribonuclease 7 (RNASE7)
• Synonyms: RNase 7; EC 3.1.27.-; Skin-derived antimicrobial protein 2; SAP-2
• Gene Name: RNASE7
• Related Disease:
  Acne vulgaris
  Adult lymphoma
  Atopic dermatitis
  Lymphoma
  Myocardial infarction
  Pediatric lymphoma
  Psoriasis
  Pyelonephritis
  Skin and skin-structure infection
  Skin disease
  Tuberculosis
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Urinary tract infection
  Vulvovaginal Candidiasis
  Neoplasm
• UniProt ID: RNAS7_HUMAN
• PDB ID: 2HKY
• EC Number: 3.1.27.-
• Pfam ID: PF00074
• Sequence:
  MAPARAGFCPLLLLLLLGLWVAEIPVSAKPKGMTSSQWFKIQHMQPSPQACNSAMKNINK
  HTKRCKDLNTFLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCR
  YKEKRQNKSYVVACKPPQKKDSQQFHLVPVHLDRVL
• Function: Exhibits a potent RNase activity. Has broad-spectrum antimicrobial activity against many pathogenic microorganisms including uropathogenic E.coli (UPEC), and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin resistant Enterococcus faecium. Causes loss of bacterial membrane integrity. Probably contributes to urinary tract sterility. Bactericidal activity is independent of RNase activity.
• Tissue Specificity: Expressed in collecting ducts in kidney, and in apical uroepithelium in bladder (at protein level) . Expressed in various epithelial tissues including skin, respiratory tract, genito-urinary tract and, at a low level, in the gut . Expressed in liver, kidney, skeletal muscle and heart .
• Reactome Pathway: Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Altered Expression	[1]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[2]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[3]
Lymphoma	DISN6V4S	Strong	Biomarker	[2]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[4]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[2]
Psoriasis	DIS59VMN	Strong	Biomarker	[5]
Pyelonephritis	DISAOX93	Strong	Altered Expression	[6]
Skin and skin-structure infection	DIS3F9EY	Strong	Biomarker	[7]
Skin disease	DISDW8R6	Strong	Biomarker	[7]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[9]
Liver cancer	DISDE4BI	moderate	Biomarker	[9]
Urinary tract infection	DISMT6UV	moderate	Biomarker	[10]
Vulvovaginal Candidiasis	DISRCR6D	moderate	Altered Expression	[11]
Neoplasm	DISZKGEW	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Ribonuclease 7 (RNASE7).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ribonuclease 7 (RNASE7).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ribonuclease 7 (RNASE7).	[16]

1 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 increases the methylation of Ribonuclease 7 (RNASE7).	[14]

References

• [1] Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.Arch Dermatol Res. 2014 Oct;306(8):689-700. doi: 10.1007/s00403-014-1477-3. Epub 2014 Jun 11.
• [2] CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells.Oncogene. 2017 Feb 16;36(7):933-941. doi: 10.1038/onc.2016.259. Epub 2016 Aug 1.
• [3] Unique profile of antimicrobial peptide expression in polymorphic light eruption lesions compared to healthy skin, atopic dermatitis, and psoriasis.Photodermatol Photoimmunol Photomed. 2018 Mar;34(2):137-144. doi: 10.1111/phpp.12355. Epub 2017 Nov 13.
• [4] Blockade of NKG2D/NKG2D ligand interaction attenuated cardiac remodelling after myocardial infarction.Cardiovasc Res. 2019 Mar 15;115(4):765-775. doi: 10.1093/cvr/cvy254.
• [5] RNase 7 downregulates TH2 cytokine production by activated human T cells.Allergy. 2017 Nov;72(11):1694-1703. doi: 10.1111/all.13173. Epub 2017 Jun 21.
• [6] Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract.Kidney Int. 2013 Apr;83(4):615-25. doi: 10.1038/ki.2012.410. Epub 2013 Jan 9.
• [7] The Antimicrobial and Immunomodulatory Function of RNase 7 in Skin.Front Immunol. 2019 Nov 5;10:2553. doi: 10.3389/fimmu.2019.02553. eCollection 2019.
• [8] RNase 7 but not psoriasin nor sPLA2-IIA associates with Mycobacterium tuberculosis during airway epithelial cell infection.Pathog Dis. 2018 Mar 1;76(2). doi: 10.1093/femspd/fty005.
• [9] Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1.Mol Cancer. 2013 Dec 18;12(1):166. doi: 10.1186/1476-4598-12-166.
• [10] Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Escherichia coli Infection.J Am Soc Nephrol. 2019 Aug;30(8):1385-1397. doi: 10.1681/ASN.2018090929. Epub 2019 Jun 25.
• [11] Differential expression of Candida albicans secreted aspartyl proteinase in human vulvovaginal candidiasis.Mycoses. 2007 Sep;50(5):383-90. doi: 10.1111/j.1439-0507.2007.01384.x.
• [12] Induction of NKG2D Ligands on Solid Tumors Requires Tumor-Specific CD8(+) T Cells and Histone Acetyltransferases.Cancer Immunol Res. 2017 Apr;5(4):300-311. doi: 10.1158/2326-6066.CIR-16-0234. Epub 2017 Feb 21.
• [13] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [14] 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.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.