Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin-protein ligase RNF19B (RNF19B)
• Synonyms: EC 2.3.2.31; IBR domain-containing protein 3; Natural killer lytic-associated molecule; RING finger protein 19B
• Gene Name: RNF19B
• Related Disease: Pneumonia
• UniProt ID: RN19B_HUMAN
• EC Number: 2.3.2.31
• Pfam ID: PF01485
• Sequence:
  MGSEKDSESPRSTSLHAAAPDPKCRSGGRRRRLTLHSVFSASARGRRARAKPQAEPPPPA
  AQPPPAPAPAAAQGPPPEALPAEPAAEAEAEAAAAAAEPGFDDEEAAEGGGPGAEEVECP
  LCLVRLPPERAPRLLSCPHRSCRDCLRHYLRLEISESRVPISCPECSERLNPHDIRLLLA
  DPPLMHKYEEFMLRRYLASDPDCRWCPAPDCGYAVIAYGCASCPKLTCEREGCQTEFCYH
  CKQIWHPNQTCDMARQQRAQTLRVRTKHTSGLSYGQESGPADDIKPCPRCSAYIIKMNDG
  SCNHMTCAVCGCEFCWLCMKEISDLHYLSPSGCTFWGKKPWSRKKKILWQLGTLIGAPVG
  ISLIAGIAIPAMVIGIPVYVGRKIHSRYEGRKTSKHKRNLAITGGVTLSVIASPVIAAVS
  VGIGVPIMLAYVYGVVPISLCRGGGCGVSTANGKGVKIEFDEDDGPITVADAWRALKNPS
  IGESSIEGLTSVLSTSGSPTDGLSVMQGPYSETASFAALSGGTLSGGILSSGKGKYSRLE
  VQADVQKEIFPKDTASLGAISDNASTRAMAGSIISSYNPQDRECNNMEIQVDIEAKPSHY
  QLVSGSSTEDSLHVHAQMAENEEEGSGGGGSEEDPPCRHQSCEQKDCLASKPWDISLAQP
  ESIRSDLESSDAQSDDVPDITSDECGSPRSHTAACPSTPRAQGAPSPSAHMNLSALAEGQ
  TVLKPEGGEARV
• Function: E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as UCKL1. Involved in the cytolytic activity of natural killer cells and cytotoxic T-cells. Protects against staurosporin-induced cell death.
• Tissue Specificity: Expressed specifically in natural killer cells, activated macrophages and cytotoxic T-cells . Present in natural killer cells (at protein level) . Ubiquitously expressed with high expression in testis .
• Reactome Pathway: Antigen processing (R-HSA-983168)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pneumonia	DIS8EF3M	Definitive	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	E3 ubiquitin-protein ligase RNF19B (RNF19B) affects the response to substance of Doxorubicin.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[2]

25 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 E3 ubiquitin-protein ligase RNF19B (RNF19B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[12]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[7]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[9]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of E3 ubiquitin-protein ligase RNF19B (RNF19B).	[17]

References

• [1] Mice deficient in NKLAM have attenuated inflammatory cytokine production in a Sendai virus pneumonia model.PLoS One. 2019 Sep 20;14(9):e0222802. doi: 10.1371/journal.pone.0222802. eCollection 2019.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines. Cancer Res. 2005 May 1;65(9):3837-45.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.