Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34M7E3)

• DOT Name: Protein farnesyltransferase subunit beta (CHURC1-FNTB)
• Synonyms: FTase-beta; EC 2.5.1.58; CAAX farnesyltransferase subunit beta; Ras proteins prenyltransferase subunit beta
• Gene Name: CHURC1-FNTB
• UniProt ID: FNTB_HUMAN
• PDB ID: 1JCQ; 1LD7; 1LD8; 1MZC; 1S63; 1SA4; 1TN6; 2F0Y; 2H6F; 2H6G; 2H6H; 2H6I; 2IEJ; 3E37
• EC Number: 2.5.1.58
• Pfam ID: PF00432
• Sequence:
  MASPSSFTYYCPPSSSPVWSEPLYSLRPEHARERLQDDSVETVTSIEQAKVEEKIQEVFS
  SYKFNHLVPRLVLQREKHFHYLKRGLRQLTDAYECLDASRPWLCYWILHSLELLDEPIPQ
  IVATDVCQFLELCQSPEGGFGGGPGQYPHLAPTYAAVNALCIIGTEEAYDIINREKLLQY
  LYSLKQPDGSFLMHVGGEVDVRSAYCAASVASLTNIITPDLFEGTAEWIARCQNWEGGIG
  GVPGMEAHGGYTFCGLAALVILKRERSLNLKSLLQWVTSRQMRFEGGFQGRCNKLVDGCY
  SFWQAGLLPLLHRALHAQGDPALSMSHWMFHQQALQEYILMCCQCPAGGLLDKPGKSRDF
  YHTCYCLSGLSIAQHFGSGAMLHDVVLGVPENALQPTHPVYNIGPDKVIQATTYFLQKPV
  PGFEELKDETSAEPATD
• Function: Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
• KEGG Pathway: Terpenoid backbone biosynthesis (hsa00900)
• Reactome Pathway:
  RAS processing (R-HSA-9648002)
  Potential therapeutics for SARS (R-HSA-9679191)
  Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[8]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[13]
Farnesol	DMV2X1B	Investigative	Farnesol decreases the expression of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Protein farnesyltransferase subunit beta (CHURC1-FNTB).	[7]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [10] 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.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.