Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6SBKQV)

• DOT Name: E3 ubiquitin-protein ligase RNF149 (RNF149)
• Synonyms: EC 2.3.2.27; DNA polymerase-transactivated protein 2; RING finger protein 149; RING-type E3 ubiquitin transferase RNF149
• Gene Name: RNF149
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RN149_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF02225 ; PF13639
• Sequence:
  MAWRRREASVGARGVLALALLALALCVPGARGRALEWFSAVVNIEYVDPQTNLTVWSVSE
  SGRFGDSSPKEGAHGLVGVPWAPGGDLEGCAPDTRFFVPEPGGRGAAPWVALVARGGCTF
  KDKVLVAARRNASAVVLYNEERYGNITLPMSHAGTGNIVVIMISYPKGREILELVQKGIP
  VTMTIGVGTRHVQEFISGQSVVFVAIAFITMMIISLAWLIFYYIQRFLYTGSQIGSQSHR
  KETKKVIGQLLLHTVKHGEKGIDVDAENCAVCIENFKVKDIIRILPCKHIFHRICIDPWL
  LDHRTCPMCKLDVIKALGYWGEPGDVQEMPAPESPPGRDPAANLSLALPDDDGSDDSSPP
  SASPAESEPQCDPSFKGDAGENTALLEAGRSDSRHGGPIS
• Function: E3 ubiquitin-protein ligase. Ubiquitinates BRAF, inducing its proteasomal degradation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]

9 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 E3 ubiquitin-protein ligase RNF149 (RNF149).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[6]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[10]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of E3 ubiquitin-protein ligase RNF149 (RNF149).	[11]

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 affects the methylation of E3 ubiquitin-protein ligase RNF149 (RNF149).	[8]

References

• [1] Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.BMC Genomics. 2018 Jun 11;19(1):450. doi: 10.1186/s12864-018-4827-2.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers. PLoS Genet. 2007 Nov;3(11):e207.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] 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.
• [7] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [8] 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.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.