Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH5FFVK)

• DOT Name: Junction-mediating and -regulatory protein (JMY)
• Gene Name: JMY
• Related Disease:
  Ankylosing spondylitis
  Breast carcinoma
  Triple negative breast cancer
• UniProt ID: JMY_HUMAN
• Pfam ID: PF15871 ; PF15920
• Sequence:
  MSFALEETLESDWVAVRPHVFDEREKHKFVFIVAWNEIEGKFAITCHNRTAQRQRSGSRE
  QAGARGGAEAGGAASDGSRGPGSPAGRGRPEATASATLVRSPGPRRSSAWAEGGSPRSTR
  SLLGDPRLRSPGSKGAESRLRSPVRAKPIPGQKTSEADDAAGAAAAAARPAPREAQVSSV
  RIVSASGTVSEEIEVLEMVKEDEAPLALSDAEQPPPATELESPAEECSWAGLFSFQDLRA
  VHQQLCSVNSQLEPCLPVFPEEPSGMWTVLFGGAPEMTEQEIDTLCYQLQVYLGHGLDTC
  GWKILSQVLFTETDDPEEYYESLSELRQKGYEEVLQRARKRIQELLDKHKNTESMVELLD
  LYQMEDEAYSSLAEATTELYQYLLQPFRDMRELAMLRRQQIKISMENDYLGPRRIESLQK
  EDADWQRKAHMAVLSIQDLTVKYFEITAKAQKAVYDRMRADQKKFGKASWAAAAERMEKL
  QYAVSKETLQMMRAKEICLEQRKHALKEEMQSLRGGTEAIARLDQLEADYYDLQLQLYEV
  QFEILKCEELLLTAQLESIKRLISEKRDEVVYYDTYESMEAMLEKEEMAASAYLQREELQ
  KLQQKARQLEARRGRVSAKKSYLRNKKEICIAKHNEKIQQRTRIEDEYRTHHTVQLKREK
  LHDEEERKSAWVSQERQRTLDRLRTFKQRYPGQVILKSTRLRLAHARRKGAASPVLQEDH
  CDSLPSVLQVEEKTEEVGEGRVKRGPSQTTEPQSLVQLEDTSLTQLEATSLPLSGVTSEL
  PPTISLPLLNNNLEPCSVTINPLPSPLPPTPPPPPPPPPPPPPPPLPVAKDSGPETLEKD
  LPRKEGNEKRIPKSASAPSAHLFDSSQLVSARKKLRKTAEGLQRRRVSSPMDEVLASLKR
  GSFHLKKVEQRTLPPFPDEDDSNNILAQIRKGVKLKKVQKDVLRESFTLLPDTDPLTRSI
  HEALRRIKEASPESEDEEEALPCTDWEN
• Function: Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions. In nucleus, acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments. Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments. Contributes to cell motility by controlling actin dynamics. May promote the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. Upon nutrient stress, directly recruited by MAP1LC3B to the phagophore membrane surfaces to promote actin assembly during autophagy. The p53/TP53-cofactor and actin activator activities are regulated via its subcellular location.
• Reactome Pathway: Regulation of TP53 Activity through Methylation (R-HSA-6804760)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[2]

3 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 Junction-mediating and -regulatory protein (JMY).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Junction-mediating and -regulatory protein (JMY).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Junction-mediating and -regulatory protein (JMY).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Junction-mediating and -regulatory protein (JMY).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Junction-mediating and -regulatory protein (JMY).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Junction-mediating and -regulatory protein (JMY).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Junction-mediating and -regulatory protein (JMY).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Junction-mediating and -regulatory protein (JMY).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Junction-mediating and -regulatory protein (JMY).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Junction-mediating and -regulatory protein (JMY).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Junction-mediating and -regulatory protein (JMY).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Junction-mediating and -regulatory protein (JMY).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Junction-mediating and -regulatory protein (JMY).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Junction-mediating and -regulatory protein (JMY).	[13]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Junction-mediating and -regulatory protein (JMY).	[14]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Junction-mediating and -regulatory protein (JMY).	[15]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Junction-mediating and -regulatory protein (JMY).	[16]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Junction-mediating and -regulatory protein (JMY).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Junction-mediating and -regulatory protein (JMY).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Junction-mediating and -regulatory protein (JMY).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Junction-mediating and -regulatory protein (JMY).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Junction-mediating and -regulatory protein (JMY).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Junction-mediating and -regulatory protein (JMY).	[24]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Junction-mediating and -regulatory protein (JMY).	[25]

References

• [1] JARID1A, JMY, and PTGER4 polymorphisms are related to ankylosing spondylitis in Chinese Han patients: a case-control study.PLoS One. 2013 Sep 19;8(9):e74794. doi: 10.1371/journal.pone.0074794. eCollection 2013.
• [2] Bio-Field Array: The Influence of Junction Mediating and Regulatory Protein Expression on Cytoskeletal Filament Behavior During Apoptosis in Triple-Negative Breast Cancer.Breast Cancer (Auckl). 2019 Feb 28;13:1178223419830981. doi: 10.1177/1178223419830981. eCollection 2019.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] 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.
• [12] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [13] 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.
• [14] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [15] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [18] 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.
• [19] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] 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.
• [21] 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.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.