Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6VVQ84)

• DOT Name: Microtubule-associated serine/threonine-protein kinase 3 (MAST3)
• Synonyms: EC 2.7.11.1
• Gene Name: MAST3
• Related Disease:
  Developmental and epileptic encephalopathy 108
  Inflammatory bowel disease
  Irritable bowel syndrome
  Rheumatoid arthritis
• UniProt ID: MAST3_HUMAN
• PDB ID: 1V9V; 3KHF
• EC Number: 2.7.11.1
• Pfam ID: PF08926 ; PF17820 ; PF00069
• Sequence:
  MDESSLLRRRGLQKELSLPRRGRGCRSGNRKSLVVGTPSPTLSRPLSPLSVPTAGSSPLD
  SPRNFSAASALNFPFARRADGRRWSLASLPSSGYGTNTPSSTLSSSSSSRERLHQLPFQP
  TPDELHFLSKHFRSSENVLDEEGGRSPRLRPRSRSLSPGRATGTFDNEIVMMNHVYRERF
  PKATAQMEGRLQEFLTAYAPGARLALADGVLGFIHHQIVELARDCLAKSGENLVTSRYFL
  EMQEKLERLLQDAHERSDSEEVSFIVQLVRKLLIIISRPARLLECLEFDPEEFYHLLEAA
  EGHAREGQGIKTDLPQYIIGQLGLAKDPLEEMVPLSHLEEEQPPAPESPESRALVGQSRR
  KPCESDFETIKLISNGAYGAVYLVRHRDTRQRFAIKKINKQNLILRNQIQQVFVERDILT
  FAENPFVVSMFCSFETRRHLCMVMEYVEGGDCATLLKNMGPLPVDMARLYFAETVLALEY
  LHNYGIVHRDLKPDNLLITSLGHIKLTDFGLSKIGLMSMATNLYEGHIEKDAREFIDKQV
  CGTPEYIAPEVIFRQGYGKPVDWWAMGVVLYEFLVGCVPFFGDTPEELFGQVVSDEIMWP
  EGDEALPADAQDLITRLLRQSPLDRLGTGGTHEVKQHPFFLALDWAGLLRHKAEFVPQLE
  AEDDTSYFDTRSERYRHLGSEDDETNDEESSTEIPQFSSCSHRFSKVYSSSEFLAVQPTP
  TFAERSFSEDREEGWERSEVDYGRRLSADIRLRSWTSSGSSCQSSSSQPERGPSPSLLNT
  ISLDTMPKFAFSSEDEGVGPGPAGPKRPVFILGEPDPPPAATPVMPKPSSLSADTAALSH
  ARLRSNSIGARHSTPRPLDAGRGRRLGGPRDPAPEKSRASSSGGSGGGSGGRVPKSASVS
  ALSLIITADDGSGGPLMSPLSPRSLSSNPSSRDSSPSRDPSPVCGSLRPPIVIHSSGKKY
  GFSLRAIRVYMGDSDVYTVHHVVWSVEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVV
  ELLLKSGNKISLRTTALENTSIKVGPARKNVAKGRMARRSKRSRRRETQDRRKSLFKKIS
  KQTSVLHTSRSFSSGLHHSLSSSESLPGSPTHSLSPSPTTPCRSPAPDVPADTTASPPSA
  SPSSSSPASPAAAGHTRPSSLHGLAAKLGPPRPKTGRRKSTSSIPPSPLACPPISAPPPR
  SPSPLPGHPPAPARSPRLRRGQSADKLGTGERLDGEAGRRTRGPEAELVVMRRLHLSERR
  DSFKKQEAVQEVSFDEPQEEATGLPTSVPQIAVEGEEAVPVALGPTGRD

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy 108	DISITA2G	Strong	Autosomal dominant	[1]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[2]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[3]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[12]

3 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 affects the methylation of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Microtubule-associated serine/threonine-protein kinase 3 (MAST3).	[10]

References

• [1] Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy. Ann Neurol. 2021 Aug;90(2):274-284. doi: 10.1002/ana.26147. Epub 2021 Jul 13.
• [2] MAST3 modulates the inflammatory response and proliferation of fibroblast-like synoviocytes in rheumatoid arthritis.Int Immunopharmacol. 2019 Dec;77:105900. doi: 10.1016/j.intimp.2019.105900. Epub 2019 Oct 20.
• [3] MAST3: a novel IBD risk factor that modulates TLR4 signaling.Genes Immun. 2008 Oct;9(7):602-12. doi: 10.1038/gene.2008.57. Epub 2008 Jul 24.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] 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.
• [11] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.