General Information of Drug Off-Target (DOT) (ID: OT81NKVT)

DOT Name MORC family CW-type zinc finger protein 3 (MORC3)
Synonyms Nuclear matrix protein 2; Zinc finger CW-type coiled-coil domain protein 3
Gene Name MORC3
Related Disease
Acute myelogenous leukaemia ( )
Autoimmune disease ( )
Dermatomyositis ( )
Idiopathic inflammatory myopathy ( )
Myositis disease ( )
Skin disease ( )
Influenza ( )
Myopathy ( )
Nasopharyngeal carcinoma ( )
UniProt ID
MORC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4QQ4; 5SVI; 5SVX; 5SVY; 6O1E; 6O5W
Pfam ID
PF13589 ; PF17942 ; PF07496
Sequence
MAAQPPRGIRLSALCPKFLHTNSTSHTWPFSAVAELIDNAYDPDVNAKQIWIDKTVINDH
ICLTFTDNGNGMTSDKLHKMLSFGFSDKVTMNGHVPVGLYGNGFKSGSMRLGKDAIVFTK
NGESMSVGLLSQTYLEVIKAEHVVVPIVAFNKHRQMINLAESKASLAAILEHSLFSTEQK
LLAELDAIIGKKGTRIIIWNLRSYKNATEFDFEKDKYDIRIPEDLDEITGKKGYKKQERM
DQIAPESDYSLRAYCSILYLKPRMQIILRGQKVKTQLVSKSLAYIERDVYRPKFLSKTVR
ITFGFNCRNKDHYGIMMYHRNRLIKAYEKVGCQLRANNMGVGVVGIIECNFLKPTHNKQD
FDYTNEYRLTITALGEKLNDYWNEMKVKKNTEYPLNLPVEDIQKRPDQTWVQCDACLKWR
KLPDGMDQLPEKWYCSNNPDPQFRNCEVPEEPEDEDLVHPTYEKTYKKTNKEKFRIRQPE
MIPRINAELLFRPTALSTPSFSSPKESVPRRHLSEGTNSYATRLLNNHQVPPQSEPESNS
LKRRLSTRSSILNAKNRRLSSQFENSVYKGDDDDEDVIILEENSTPKPAVDHDIDMKSEQ
SHVEQGGVQVEFVGDSEPCGQTGSTSTSSSRCDQGNTAATQTEVPSLVVKKEETVEDEID
VRNDAVILPSCVEAEAKIHETQETTDKSADDAGCQLQELRNQLLLVTEEKENYKRQCHMF
TDQIKVLQQRILEMNDKYVKKETCHQSTETDAVFLLESINGKSESPDHMVSQYQQALEEI
ERLKKQCSALQHVKAECSQCSNNESKSEMDEMAVQLDDVFRQLDKCSIERDQYKSEVELL
EMEKSQIRSQCEELKTEVEQLKSTNQQTATDVSTSSNIEESVNHMDGESLKLRSLRVNVG
QLLAMIVPDLDLQQVNYDVDVVDEILGQVVEQMSEISST
Function
Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response. Mechanistically, possesses a primary antiviral function through a MORC3-regulated element that activates IFNB1, and this function is guarded by a secondary IFN-repressing function. Sumoylated MORC3-NBs associates with PML-NBs and recruits TP53 and SP100, thus regulating TP53 activity. Binds RNA in vitro. Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3. The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 ; (Microbial infection) May be required for influenza A transcription during viral infection.
Tissue Specificity Expressed in heart, placenta, skeletal muscle, brain, pancreas, lung, liver, but not kidney.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Autoimmune disease DISORMTM Strong Biomarker [2]
Dermatomyositis DIS50C5O Strong Biomarker [3]
Idiopathic inflammatory myopathy DISGB1BZ Strong Biomarker [4]
Myositis disease DISCIXF0 Strong Biomarker [5]
Skin disease DISDW8R6 Strong Biomarker [6]
Influenza DIS3PNU3 moderate Biomarker [7]
Myopathy DISOWG27 Limited Biomarker [8]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [8]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 MORC family CW-type zinc finger protein 3 (MORC3). [9]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [10]
Tretinoin DM49DUI Approved Tretinoin increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [11]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [12]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [13]
Decitabine DMQL8XJ Approved Decitabine increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [14]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of MORC family CW-type zinc finger protein 3 (MORC3). [15]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of MORC family CW-type zinc finger protein 3 (MORC3). [22]
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⏷ Show the Full List of 10 Drug(s)
4 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 MORC family CW-type zinc finger protein 3 (MORC3). [17]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of MORC family CW-type zinc finger protein 3 (MORC3). [18]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of MORC family CW-type zinc finger protein 3 (MORC3). [20]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of MORC family CW-type zinc finger protein 3 (MORC3). [21]
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References

1 Anti-NXP2-antibody-positive immune-mediated necrotizing myopathy associated with acute myeloid leukemia: A case report.Medicine (Baltimore). 2018 Jul;97(28):e11501. doi: 10.1097/MD.0000000000011501.
2 Mechanism for autoinhibition and activation of the MORC3 ATPase.Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6111-6119. doi: 10.1073/pnas.1819524116. Epub 2019 Mar 8.
3 Perimysial microarteriopathy in dermatomyositis with anti-nuclear matrix protein-2 antibodies.Eur J Neurol. 2020 Mar;27(3):514-521. doi: 10.1111/ene.14097. Epub 2019 Oct 25.
4 Association of anti-nuclear matrix protein 2 antibody with complications in patients with idiopathic inflammatory myopathies: A meta-analysis of 20 cohorts.Clin Immunol. 2019 Jan;198:11-18. doi: 10.1016/j.clim.2018.11.008. Epub 2018 Nov 13.
5 Current understanding and recent advances in myositis-specific and -associated autoantibodies detected in patients with dermatomyositis.Expert Rev Clin Immunol. 2020 Jan;16(1):79-89. doi: 10.1080/1744666X.2019.1699059. Epub 2019 Dec 8.
6 Cutaneous and Systemic Findings Associated With Nuclear Matrix Protein 2 Antibodies in Adult Dermatomyositis Patients.Arthritis Care Res (Hoboken). 2017 Dec;69(12):1909-1914. doi: 10.1002/acr.23210. Epub 2017 Nov 2.
7 MORC3 Is a Target of the Influenza A Viral Protein NS1.Structure. 2019 Jun 4;27(6):1029-1033.e3. doi: 10.1016/j.str.2019.03.015. Epub 2019 Apr 18.
8 Calcinosis and malignancy are rare in Chinese adult patients with myositis and nuclear matrix protein 2 antibodies identified by an unlabeled immunoprecipitation assay.Clin Rheumatol. 2018 Oct;37(10):2731-2739. doi: 10.1007/s10067-018-4216-x. Epub 2018 Jul 23.
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 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.
12 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.
13 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
14 The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
15 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.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 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.
18 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.
19 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.
20 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
21 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.
22 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.