Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIK1RY)

DOT Name Ribonuclease K6 (RNASE6)
Synonyms RNase K6; EC 3.1.27.-
Gene Name RNASE6
UniProt ID
RNAS6_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4X09; 5OAB; 6ENP; 6MV6; 6MV7
EC Number
3.1.27.-
Pfam ID
PF00074
Sequence
MVLCFPLLLLLLVLWGPVCPLHAWPKRLTKAHWFEIQHIQPSPLQCNRAMSGINNYTQHC
KHQNTFLHDSFQNVAAVCDLLSIVCKNRRHNCHQSSKPVNMTDCRLTSGKYPQCRYSAAA
QYKFFIVACDPPQKSDPPYKLVPVHLDSIL
Function
Ribonuclease which shows a preference for the pyrimidines uridine and cytosine. Has potent antibacterial activity against a range of Gram-positive and Gram-negative bacteria, including P.aeruginosa, A.baumanii, M.luteus, S.aureus, E.faecalis, E.faecium, S.saprophyticus and E.coli. Causes loss of bacterial membrane integrity, and also promotes agglutination of Gram-negative bacteria. Probably contributes to urinary tract sterility. Bactericidal activity is independent of RNase activity.
Tissue Specificity
Highly expressed in spleen (at protein level) . Has little or no expression in healthy kidneys (at protein level) . Detected in interstitial leukocytes in infected kidneys (at protein level) . Expressed in ureter where it localizes to urothelial and submucosal leukocytes (at protein level) . Strong expression in lung and thymus, and lower expression in heart, placenta, pancreas, liver, brain and skeletal muscle . Also expressed in monocytes and neutrophils .
Reactome Pathway
Antimicrobial peptides (R-HSA-6803157 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Ribonuclease K6 (RNASE6). [1]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Ribonuclease K6 (RNASE6). [2]
Aspirin DM672AH Approved Aspirin increases the expression of Ribonuclease K6 (RNASE6). [3]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Ribonuclease K6 (RNASE6). [4]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Ribonuclease K6 (RNASE6). [5]
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References

1 Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
2 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.
3 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
4 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
5 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.