Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT89V4N5)

• DOT Name: E3 ubiquitin-protein ligase MARCHF3 (MARCHF3)
• Synonyms: EC 2.3.2.27; Membrane-associated RING finger protein 3; Membrane-associated RING-CH protein III; MARCH-III; RING finger protein 173; RING-type E3 ubiquitin transferase MARCHF3
• Gene Name: MARCHF3
• Related Disease:
  Asthma
  Invasive breast carcinoma
  Advanced cancer
  Endometrial cancer
  Endometrial carcinoma
  Non-small-cell lung cancer
  Ulcerative colitis
  Congenital heart disease
  Hyperglycemia
  Type-1/2 diabetes
• UniProt ID: MARH3_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF12906
• Sequence:
  MTTSRCSHLPEVLPDCTSSAAPVVKTVEDCGSLVNGQPQYVMQVSAKDGQLLSTVVRTLA
  TQSPFNDRPMCRICHEGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTSYCELCHFRF
  AVERKPRPLVEWLRNPGPQHEKRTLFGDMVCFLFITPLATISGWLCLRGAVDHLHFSSRL
  EAVGLIALTVALFTIYLFWTLVSFRYHCRLYNEWRRTNQRVILLIPKSVNVPSNQPSLLG
  LHSVKRNSKETVV
• Function: E3 ubiquitin-protein ligase which may be involved in endosomal trafficking. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Invasive breast carcinoma	DISANYTW	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[4]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[6]
Congenital heart disease	DISQBA23	Limited	Biomarker	[7]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[8]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[15]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[17]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[18]
Malathion	DMXZ84M	Approved	Malathion increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[24]

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 E3 ubiquitin-protein ligase MARCHF3 (MARCHF3).	[21]

References

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• [2] Breast Cancer Recurrence in the Nipple-Areola Complex After Nipple-Sparing Mastectomy With Immediate Breast Reconstruction for Invasive Breast Cancer.JAMA Surg. 2019 Nov 1;154(11):1030-1037. doi: 10.1001/jamasurg.2019.2959.
• [3] Comparison and screening of different risk assessment models for deep vein thrombosis in patients with solid tumors.J Thromb Thrombolysis. 2019 Aug;48(2):292-298. doi: 10.1007/s11239-019-01840-x.
• [4] Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.JAMA. 2017 Mar 28;317(12):1224-1233. doi: 10.1001/jama.2017.2068.
• [5] Stereotactic Ablative Radiotherapy Combined with Immune Checkpoint Inhibitors Reboots the Immune Response Assisted by Immunotherapy in Metastatic Lung Cancer: A Systematic Review.Int J Mol Sci. 2019 May 2;20(9):2173. doi: 10.3390/ijms20092173.
• [6] Efficacy and safety of Kangfuxin liquid combined with aminosalicylic acid for the treatment of ulcerative colitis: A systematic review and meta-analysis.Medicine (Baltimore). 2018 May;97(21):e10807. doi: 10.1097/MD.0000000000010807.
• [7] Palliative Care Opportunities Among Adults With Congenital Heart Disease-A Systematic Review.J Pain Symptom Manage. 2019 Nov;58(5):891-898. doi: 10.1016/j.jpainsymman.2019.07.025. Epub 2019 Aug 9.
• [8] Nop-7-associated 2 (NSA2), a candidate gene for diabetic nephropathy, is involved in the TGF1 pathway.Int J Biochem Cell Biol. 2013 Mar;45(3):626-35. doi: 10.1016/j.biocel.2012.11.020. Epub 2012 Dec 7.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] 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.
• [17] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [18] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [19] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] 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.
• [22] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.