Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG9SF10)

• DOT Name: E3 ubiquitin-protein ligase MARCHF7 (MARCHF7)
• Synonyms: EC 2.3.2.27; Axotrophin; Membrane-associated RING finger protein 7; Membrane-associated RING-CH protein VII; MARCH-VII; RING finger protein 177; RING-type E3 ubiquitin transferase MARCHF7
• Gene Name: MARCHF7
• Related Disease:
  Neoplasm
  Tuberculosis
  Cervical cancer
  Cervical carcinoma
  Crohn disease
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Impulse control disorder
  Late-onset Parkinson disease
  Ovarian cancer
  Ovarian neoplasm
  Sarcoidosis
  Graft-versus-host disease
  Leukemia
• UniProt ID: MARH7_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF12906
• Sequence:
  MESKPSRIPRRISVQPSSSLSARMMSGSRGSSLNDTYHSRDSSFRLDSEYQSTSASASAS
  PFQSAWYSESEITQGARSRSQNQQRDHDSKRPKLSCTNCTTSAGRNVGNGLNTLSDSSWR
  HSQVPRSSSMVLGSFGTDLMRERRDLERRTDSSISNLMDYSHRSGDFTTSSYVQDRVPSY
  SQGARPKENSMSTLQLNTSSTNHQLPSEHQTILSSRDSRNSLRSNFSSRESESSRSNTQP
  GFSYSSSRDEAPIISNSERVVSSQRPFQESSDNEGRRTTRRLLSRIASSMSSTFFSRRSS
  QDSLNTRSLNSENSYVSPRILTASQSRSNVPSASEVPDNRASEASQGFRFLRRRWGLSSL
  SHNHSSESDSENFNQESEGRNTGPWLSSSLRNRCTPLFSRRRREGRDESSRIPTSDTSSR
  SHIFRRESNEVVHLEAQNDPLGAAANRPQASAASSSATTGGSTSDSAQGGRNTGISGILP
  GSLFRFAVPPALGSNLTDNVMITVDIIPSGWNSADGKSDKTKSAPSRDPERLQKIKESLL
  LEDSEEEEGDLCRICQMAAASSSNLLIEPCKCTGSLQYVHQDCMKKWLQAKINSGSSLEA
  VTTCELCKEKLELNLEDFDIHELHRAHANEQAEYEFISSGLYLVVLLHLCEQSFSDMMGN
  TNEPSTRVRFINLARTLQAHMEDLETSEDDSEEDGDHNRTFDIA
• Function: E3 ubiquitin-protein ligase which may specifically enhance the E2 activity of HIP2. 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 be involved in T-cell proliferation by regulating LIF secretion. May play a role in lysosome homeostasis. Promotes 'Lys-6', 'Lys-11' and 'Lys-63'-linked mixed polyubiquitination on ATG14 leading to the inhibition of autophagy by impairing the interaction between ATG14 and STX7. Participates in the dopamine-mediated negative regulation of the NLRP3 inflammasome by promoting its uibiquitination and subsequent degradation.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[4]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Impulse control disorder	DISRIYJ5	Strong	Biomarker	[6]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Sarcoidosis	DISE5B8Z	Strong	Biomarker	[7]
Graft-versus-host disease	DIS0QADF	moderate	Altered Expression	[8]
Leukemia	DISNAKFL	moderate	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[13]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[18]

2 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 decreases the methylation of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of E3 ubiquitin-protein ligase MARCHF7 (MARCHF7).	[16]

References

• [1] miR-27b-3p/MARCH7 regulates invasion and metastasis of endometrial cancer cells through Snail-mediated pathway.Acta Biochim Biophys Sin (Shanghai). 2019 May 23;51(5):492-500. doi: 10.1093/abbs/gmz030.
• [2] "The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.Vaccine. 2017 Jun 14;35(27):3433-3440. doi: 10.1016/j.vaccine.2017.04.007. Epub 2017 May 2.
• [3] Ubiquitin E3 Ligase MARCH7 promotes proliferation and invasion of cervical cancer cells through VAV2-RAC1-CDC42 pathway.Oncol Lett. 2018 Aug;16(2):2312-2318. doi: 10.3892/ol.2018.8908. Epub 2018 Jun 5.
• [4] Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study.Lancet Gastroenterol Hepatol. 2019 May;4(5):341-353. doi: 10.1016/S2468-1253(19)30012-3. Epub 2019 Feb 27.
• [5] Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer.Cell Physiol Biochem. 2018;47(2):654-666. doi: 10.1159/000490020. Epub 2018 May 22.
• [6] Dopaminergic Neurotransmission in Patients With Parkinson's Disease and Impulse Control Disorders: A Systematic Review and Meta-Analysis of PET and SPECT Studies.Front Neurol. 2018 Dec 4;9:1018. doi: 10.3389/fneur.2018.01018. eCollection 2018.
• [7] FDG PET/CT Course of Pembrolizumab-Associated Multiorgan Sarcoidosis.Clin Nucl Med. 2019 Feb;44(2):167-168. doi: 10.1097/RLU.0000000000002408.
• [8] Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance.Int Immunopharmacol. 2006 Dec 20;6(13-14):1993-2001. doi: 10.1016/j.intimp.2006.09.015. Epub 2006 Oct 17.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [15] 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.
• [16] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [17] 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.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.