Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTONIS87)

DOT Name Protein phosphatase 1 regulatory subunit 12B (PPP1R12B)
Synonyms Myosin phosphatase-targeting subunit 2; Myosin phosphatase target subunit 2
Gene Name PPP1R12B
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Breast lobular carcinoma ( )
Breast neoplasm ( )
Coeliac disease ( )
Colorectal carcinoma ( )
Neoplasm ( )
Prion disease ( )
Asthma ( )
UniProt ID
MYPT2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12796 ; PF15898
Sequence
MAELEHLGGKRAESARMRRAEQLRRWRGSLTEQEPAERRGAGRQPLTRRGSPRVRFEDGA
VFLAACSSGDTDEVRKLLARGADINTVNVDGLTALHQACIDENLDMVKFLVENRANVNQQ
DNEGWTPLHAAASCGYLNIAEYFINHGASVGIVNSEGEVPSDLAEEPAMKDLLLEQVKKQ
GVDLEQSRKEEEQQMLQDARQWLNSGKIEDVRQARSGATALHVAAAKGYSEVLRLLIQAG
YELNVQDYDGWTPLHAAAHWGVKEACSILAEALCDMDIRNKLGQTPFDVADEGLVEHLEL
LQKKQNVLRSEKETRNKLIESDLNSKIQSGFFKNKEKMLYEEETPKSQEMEEENKESSSS
SSEEEEGEDEASESETEKEADKKPEAFVNHSNSESKSSITEQIPAPAQNTFSASSARRFS
SGLFNKPEEPKDESPSSWRLGLRKTGSHNMLSEVANSREPIRDRGSSIYRSSSSPRISAL
LDNKDKERENKSYISSLAPRKLNSTSDIEEKENRESAVNLVRSGSYTRQLWRDEAKGNEI
PQTIAPSTYVSTYLKRTPHKSQADTTAEKTADNVSSSTPLCVITNRPLPSTANGVTATPV
LSITGTDSSVEAREKRRSYLTPVRDEEAESLRKARSRQARQTRRSTQGVTLTDLQEAERT
FSRSRAERQAQEQPREKPTDTEGLEGSPEKHEPSAVPATEAGEGQQPWGRSLDEEPICHR
LRCPAQPDKPTTPASPSTSRPSLYTSSHLLWTNRFSVPDSESSETTTNTTTAKEMDKNEN
EEADLDEQSSKRLSIRERRRPKERRRGTGINFWTKDEDETDGSEEVKETWHERLSRLESG
GSNPTTSDSYGDRASARARREAREARLATLTSRVEEDSNRDYKKLYESALTENQKLKTKL
QEAQLELADIKSKLEKVAQQKQEKTSDRSSVLEMEKRERRALERKMSEMEEEMKVLTELK
SDNQRLKDENGALIRVISKLSK
Function Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus.
Tissue Specificity Detected in skeletal muscle, fetal and adult heart, brain, placenta, kidney, spleen, thymus, pancreas and lung. Isoform 3 and isoform 4 are heart specific.
KEGG Pathway
Vascular smooth muscle contraction (hsa04270 )
Focal adhesion (hsa04510 )
Regulation of actin cytoskeleton (hsa04810 )
Oxytocin sig.ling pathway (hsa04921 )
Proteoglycans in cancer (hsa05205 )
Reactome Pathway
RHO GTPases activate CIT (R-HSA-5625900 )
RHO GTPases Activate ROCKs (R-HSA-5627117 )
RHO GTPases activate PAKs (R-HSA-5627123 )
RHO GTPases activate PKNs (R-HSA-5625740 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Breast lobular carcinoma DISBY98Q Strong Biomarker [1]
Breast neoplasm DISNGJLM Strong Biomarker [1]
Coeliac disease DISIY60C Strong Altered Expression [2]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [3]
Neoplasm DISZKGEW Strong Biomarker [3]
Prion disease DISOUMB0 Strong Genetic Variation [4]
Asthma DISW9QNS moderate 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
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [9]
Marinol DM70IK5 Approved Marinol increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [10]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [11]
Fenfluramine DM0762O Phase 3 Fenfluramine increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [12]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [13]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [16]
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⏷ Show the Full List of 10 Drug(s)
1 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 Protein phosphatase 1 regulatory subunit 12B (PPP1R12B). [15]
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References

1 Insertional mutagenesis identifies drivers of a novel oncogenic pathway in invasive lobular breast carcinoma.Nat Genet. 2017 Aug;49(8):1219-1230. doi: 10.1038/ng.3905. Epub 2017 Jun 26.
2 Genes involved in muscle contractility and nutrient signaling pathways within celiac disease risk loci show differential mRNA expression.BMC Med Genet. 2015 Jun 30;16:44. doi: 10.1186/s12881-015-0190-1.
3 The PEAK1-PPP1R12B axis inhibits tumor growth and metastasis by regulating Grb2/PI3K/Akt signalling in colorectal cancer.Cancer Lett. 2019 Feb 1;442:383-395. doi: 10.1016/j.canlet.2018.11.014. Epub 2018 Nov 22.
4 Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Hum Mol Genet. 2012 Apr 15;21(8):1897-906. doi: 10.1093/hmg/ddr607. Epub 2011 Dec 30.
5 [Genome-wide association study of allergic diseases in Russians of Western Siberia].Mol Biol (Mosk). 2011 May-Jun;45(3):464-72.
6 Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
11 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
12 Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
13 A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
14 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.
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 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.