Details of Drug Off-Target (DOT)

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

• DOT Name: E3 ubiquitin-protein ligase MARCHF11 (MARCHF11)
• Synonyms: EC 2.3.2.27; Membrane-associated RING finger protein 11; Membrane-associated RING-CH protein XI; MARCH-XI; RING-type E3 ubiquitin transferase MARCHF11
• Gene Name: MARCHF11
• Related Disease:
  Alcohol use disorder
  Drug dependence
  Insomnia
  Neoplasm
  Optic neuritis
  Osteoporosis
  Postpartum depression
  Post-traumatic stress disorder
  Rectal carcinoma
• UniProt ID: MARHB_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF12906
• Sequence:
  MSFEGGHGGSRCRGAESGDAEPPPQPPPPPPPTPPPGEPAPVPAAPRYLPPLPASPETPE
  RAAGPSEPLGEVAPRCRGADELPPPPLPLQPAGQEVAAAGDSGEGPRRLPEAAAAKGGPG
  ESEAGAGGERERRGAGDQPETRSVCSSRSSSSGGGDQRAGHQHQHHQPICKICFQGAEQG
  ELLNPCRCDGSVRYTHQLCLLKWISERGSWTCELCCYRYHVIAIKMKQPCQWQSISITLV
  EKVQMIAVILGSLFLIASVTWLLWSAFSPYAVWQRKDILFQICYGMYGFMDLVCIGLIVH
  EGAAVYRVFKRWRAVNLHWDVLNYDKATDIEESSRGESSTSRTLWLPLTALRNRNLVHPT
  QLTSPRFQCGYVLLHLFNRMRPHEDLSEDNSSGEVVMRVTSV
• Function: E3 ubiquitin-protein ligase that mediates polyubiquitination of CD4. 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. May play a role in ubuquitin-dependent protein sorting in developmenting spermatids.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol use disorder	DISMB65Y	Definitive	Biomarker	[1]
Drug dependence	DIS9IXRC	Strong	Genetic Variation	[2]
Insomnia	DIS0AFR7	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Optic neuritis	DISDYCHC	Strong	Biomarker	[5]
Osteoporosis	DISF2JE0	Strong	Biomarker	[6]
Postpartum depression	DIS08UKE	Strong	Biomarker	[7]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[8]
Rectal carcinoma	DIS8FRR7	Limited	Biomarker	[9]

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 MARCHF11 (MARCHF11).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of E3 ubiquitin-protein ligase MARCHF11 (MARCHF11).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of E3 ubiquitin-protein ligase MARCHF11 (MARCHF11).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of E3 ubiquitin-protein ligase MARCHF11 (MARCHF11).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of E3 ubiquitin-protein ligase MARCHF11 (MARCHF11).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 ubiquitin-protein ligase MARCHF11 (MARCHF11).	[14]

References

• [1] Risk Factors for Problem Drinking among Evacuees in Fukushima following the Great East Japan Earthquake: The Fukushima Health Management Survey.Tohoku J Exp Med. 2019 Aug;248(4):239-252. doi: 10.1620/tjem.248.239.
• [2] The levels of triglyceride and total cholesterol in methamphetamine dependence.Medicine (Baltimore). 2017 Apr;96(16):e6631. doi: 10.1097/MD.0000000000006631.
• [3] Longitudinal trends in disaster-related insomnia among Fukushima nuclear plant workers: the Fukushima Nuclear Energy Workers' Support Project study.Sleep. 2019 May 1;42(5):zsz043. doi: 10.1093/sleep/zsz043.
• [4] Benefit-Risk Summary of Crizotinib for the Treatment of Patients With ROS1 Alteration-Positive, Metastatic Non-Small Cell Lung Cancer.Oncologist. 2016 Aug;21(8):974-80. doi: 10.1634/theoncologist.2016-0101. Epub 2016 Jun 21.
• [5] Anatomical Wiring and Functional Networking Changes in the Visual System Following Optic Neuritis.JAMA Neurol. 2018 Mar 1;75(3):287-295. doi: 10.1001/jamaneurol.2017.3880.
• [6] AGS and NIA Bench-to Bedside Conference Summary: Osteoporosis and Soft Tissue (Muscle and Fat) Disorders.J Am Geriatr Soc. 2020 Jan;68(1):31-38. doi: 10.1111/jgs.16248. Epub 2019 Dec 2.
• [7] Postpartum depression among women in Nagoya indirectly exposed to the Great East Japan Earthquake.Sci Rep. 2018 Aug 2;8(1):11624. doi: 10.1038/s41598-018-30065-w.
• [8] Criticism by community people and poor workplace communication as risk factors for the mental health of local welfare workers after the Great East Japan Earthquake: A cross-sectional study.PLoS One. 2017 Nov 22;12(11):e0185930. doi: 10.1371/journal.pone.0185930. eCollection 2017.
• [9] Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer: A Phase II Open Label Prospective Randomized Controlled Trial.Ann Surg. 2018 Feb;267(2):243-251. doi: 10.1097/SLA.0000000000002321.
• [10] 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.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] 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.
• [14] 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.