Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3MRK62)

DOT Name Protein arginine N-methyltransferase 8 (PRMT8)
Synonyms EC 2.1.1.319; Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4
Gene Name PRMT8
Related Disease
Cervical cancer ( )
Cervical carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Ewing sarcoma ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Amyotrophic lateral sclerosis ( )
UniProt ID
ANM8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4X41; 5DST
EC Number
2.1.1.319
Pfam ID
PF06325
Sequence
MGMKHSSRCLLLRRKMAENAAESTEVNSPPSQPPQPVVPAKPVQCVHHVSTQPSCPGRGK
MSKLLNPEEMTSRDYYFDSYAHFGIHEEMLKDEVRTLTYRNSMYHNKHVFKDKVVLDVGS
GTGILSMFAAKAGAKKVFGIECSSISDYSEKIIKANHLDNIITIFKGKVEEVELPVEKVD
IIISEWMGYCLFYESMLNTVIFARDKWLKPGGLMFPDRAALYVVAIEDRQYKDFKIHWWE
NVYGFDMTCIRDVAMKEPLVDIVDPKQVVTNACLIKEVDIYTVKTEELSFTSAFCLQIQR
NDYVHALVTYFNIEFTKCHKKMGFSTAPDAPYTHWKQTVFYLEDYLTVRRGEEIYGTISM
KPNAKNVRDLDFTVDLDFKGQLCETSVSNDYKMR
Function
S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dimer. Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.
Tissue Specificity Brain-specific.
BioCyc Pathway
MetaCyc:ENSG00000111218-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cervical cancer DISFSHPF Strong Altered Expression [1]
Cervical carcinoma DIST4S00 Strong Altered Expression [1]
Colon cancer DISVC52G Strong Altered Expression [2]
Colon carcinoma DISJYKUO Strong Altered Expression [2]
Colonic neoplasm DISSZ04P Strong Biomarker [2]
Ewing sarcoma DISQYLV3 Strong Posttranslational Modification [3]
Adult glioblastoma DISVP4LU moderate Biomarker [4]
Glioblastoma multiforme DISK8246 moderate Biomarker [4]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [5]
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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
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Protein arginine N-methyltransferase 8 (PRMT8). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Protein arginine N-methyltransferase 8 (PRMT8). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein arginine N-methyltransferase 8 (PRMT8). [10]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Berberine DMC5Q8X Phase 4 Berberine increases the expression of Protein arginine N-methyltransferase 8 (PRMT8). [8]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Protein arginine N-methyltransferase 8 (PRMT8). [9]
Ribavirin DMEYLH9 Phase 1 Trial Ribavirin decreases the expression of Protein arginine N-methyltransferase 8 (PRMT8). [11]
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References

1 PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.Oncol Lett. 2017 Mar;13(3):1983-1989. doi: 10.3892/ol.2017.5671. Epub 2017 Feb 1.
2 Protein arginine methyltransferase 8 gene enhances the colon cancer stem cell (CSC) function by upregulating the pluripotency transcription factor.J Cancer. 2018 Apr 6;9(8):1394-1402. doi: 10.7150/jca.23835. eCollection 2018.
3 Identification of proteins interacting with protein arginine methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of its methylation state.Proteins. 2008 Sep;72(4):1125-37. doi: 10.1002/prot.22004.
4 PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology.Stem Cells. 2015 Mar;33(3):726-41. doi: 10.1002/stem.1894.
5 Protein arginine methyltransferase 1 and 8 interact with FUS to modify its sub-cellular distribution and toxicity in vitro and in vivo.PLoS One. 2013 Apr 19;8(4):e61576. doi: 10.1371/journal.pone.0061576. Print 2013.
6 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.
7 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
8 Berberine acts as a putative epigenetic modulator by affecting the histone code. Toxicol In Vitro. 2016 Oct;36:10-17. doi: 10.1016/j.tiv.2016.06.004. Epub 2016 Jun 13.
9 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.
10 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.
11 Ribavirin inhibits the growth and ascites formation of hepatocellular carcinoma through downregulation of type I CARM1 and type II PRMT5. Toxicol Appl Pharmacol. 2022 Jan 15;435:115829. doi: 10.1016/j.taap.2021.115829. Epub 2021 Dec 14.