Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8K2X8P)

DOT Name	Microspherule protein 1 (MCRS1)
Synonyms	58 kDa microspherule protein; Cell cycle-regulated factor p78; INO80 complex subunit J; MCRS2
Gene Name	MCRS1
Related Disease	Glioma ( ) Adult glioblastoma ( ) Advanced cancer ( ) Alopecia ( ) Alopecia areata ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Esophageal squamous cell carcinoma ( ) Fibrosarcoma ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Gonorrhea ( ) Herpes simplex infection ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Neoplasm ( ) Renal cell carcinoma ( ) Stomach cancer ( ) Chronic obstructive pulmonary disease ( ) Hepatocellular carcinoma ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( )
UniProt ID	MCRS1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00498 ; PF13325
Sequence	MDKDSQGLLDSSLMASGTASRSEDEESLAGQKRASSQALGTIPKRRSSSRFIKRKKFDDE LVESSLAKSSTRAKGASGVEPGRCSGSEPSSSEKKKVSKAPSTPVPPSPAPAPGLTKRVK KSKQPLQVTKDLGRWKPADDLLLINAVLQTNDLTSVHLGVKFSCRFTLREVQERWYALLY DPVISKLACQAMRQLHPEAIAAIQSKALFSKAEEQLLSKVGSTSQPTLETFQDLLHRHPD AFYLARTAKALQAHWQLMKQYYLLEDQTVQPLPKGDQVLNFSDAEDLIDDSKLKDMRDEV LEHELMVADRRQKREIRQLEQELHKWQVLVDSITGMSSPDFDNQTLAVLRGRMVRYLMRS REITLGRATKDNQIDVDLSLEGPAWKISRKQGVIKLKNNGDFFIANEGRRPIYIDGRPVL CGSKWRLSNNSVVEIASLRFVFLINQDLIALIRAEAAKITPQ
Function	Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity. Binds to G-quadruplex structures in mRNA. Binds to RNA homomer poly(G) and poly(U).
Tissue Specificity	Detected in testis, and at lower levels in spleen, thymus, prostate, uterus, small intestine, colon and leukocytes.
KEGG Pathway	ATP-dependent chromatin remodeling (hsa03082 )
Reactome Pathway	UCH proteinases (R-HSA-5689603 ) DNA Damage Recognition in GG-NER (R-HSA-5696394 ) Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755 ) HATs acetylate histones (R-HSA-3214847 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alopecia	DIS37HU4	Strong	Biomarker	[4]
Alopecia areata	DIS0XXBJ	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[6]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[7]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Gonorrhea	DISQ5AO6	Strong	Biomarker	[7]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[7]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[12]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[14]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 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 Microspherule protein 1 (MCRS1).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microspherule protein 1 (MCRS1).	[20]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Selenium	DM25CGV	Approved	Selenium increases the expression of Microspherule protein 1 (MCRS1).	[16]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Microspherule protein 1 (MCRS1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Microspherule protein 1 (MCRS1).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Microspherule protein 1 (MCRS1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microspherule protein 1 (MCRS1).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Microspherule protein 1 (MCRS1).	[21]
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References

1	Expression of 58-kD Microspherule Protein (MSP58) is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients.Cell Physiol Biochem. 2016;38(2):635-45. doi: 10.1159/000438656. Epub 2016 Feb 8.
2	RNAi-mediated inhibition of MSP58 decreases tumour growth, migration and invasion in a human glioma cell line.J Cell Mol Med. 2009 Nov-Dec;13(11-12):4608-22. doi: 10.1111/j.1582-4934.2008.00499.x.
3	Knockdown of MSP58 inhibits the proliferation and metastasis in human renal cell carcinoma cells.Biomed Pharmacother. 2017 Jul;91:54-59. doi: 10.1016/j.biopha.2017.04.036. Epub 2017 May 23.
4	Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region.Hum Genet. 2000 Jun;106(6):639-45. doi: 10.1007/s004390000318.
5	MSP58 knockdown inhibits the proliferation of esophageal squamous cell carcinoma in vitro and in vivo.Asian Pac J Cancer Prev. 2012;13(7):3233-8. doi: 10.7314/apjcp.2012.13.7.3233.
6	58-kDa microspherule protein (MSP58) is novel Brahma-related gene 1 (BRG1)-associated protein that modulates p53/p21 senescence pathway.J Biol Chem. 2012 Jun 29;287(27):22533-48. doi: 10.1074/jbc.M111.335331. Epub 2012 May 4.
7	Effects of MCRS1 on proliferation, migration, invasion, and epithelial mesenchymal transition of gastric cancer cells by interacting with Pkmyt1 protein kinase.Cell Signal. 2019 Jul;59:171-181. doi: 10.1016/j.cellsig.2019.04.002. Epub 2019 Apr 3.
8	TOJ3, a target of the v-Jun transcription factor, encodes a protein with transforming activity related to human microspherule protein 1 (MCRS1).Oncogene. 2001 Nov 8;20(51):7524-35. doi: 10.1038/sj.onc.1204938.
9	Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer.Genes Chromosomes Cancer. 2013 Mar;52(3):305-15. doi: 10.1002/gcc.22030. Epub 2012 Dec 8.
10	MCRS1 overexpression, which is specifically inhibited by miR-129*, promotes the epithelial-mesenchymal transition and metastasis in non-small cell lung cancer.Mol Cancer. 2014 Nov 6;13:245. doi: 10.1186/1476-4598-13-245.
11	A candidate gene identification strategy utilizing mouse to human big-data mining: "3R-tenet" in COPD genetic research.Respir Res. 2018 Jun 6;19(1):92. doi: 10.1186/s12931-018-0795-y.
12	miR-186 modulates hepatocellular carcinoma cell proliferation and mobility via targeting MCRS1-mediated Wnt/-catenin signaling.J Cell Physiol. 2019 Dec;234(12):23135-23145. doi: 10.1002/jcp.28878. Epub 2019 May 29.
13	Downregulation of MSP58 suppresses cell proliferation in neuroblastoma cell lines.Neuroreport. 2012 Nov 14;23(16):932-6. doi: 10.1097/WNR.0b013e328359566e.
14	The candidate oncogene (MCRS1) promotes the growth of human lung cancer cells via the miR-155-Rb1 pathway.J Exp Clin Cancer Res. 2015 Oct 14;34:121. doi: 10.1186/s13046-015-0235-5.
15	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.
16	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
17	Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
18	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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	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.