Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5WUD4C)

• DOT Name: Microtubule-associated protein 1S (MAP1S)
• Synonyms: MAP-1S; BPY2-interacting protein 1; Microtubule-associated protein 8; Variable charge Y chromosome 2-interacting protein 1; VCY2-interacting protein 1; VCY2IP-1
• Gene Name: MAP1S
• Related Disease:
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Crohn disease
  Giant axonal neuropathy 1
  Huntington disease
  Kidney failure
  Renal cell carcinoma
  Renal fibrosis
  Adenocarcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Coronary heart disease
  Hepatocellular carcinoma
  Liver cancer
  Pancreatic ductal carcinoma
  Prostate cancer
  Prostate carcinoma
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Cardiac disease
  Neoplasm
  Parkinson disease
• UniProt ID: MAP1S_HUMAN
• Sequence:
  MAAVAGSGAAAAPSSLLLVVGSEFGSPGLLTYVLEELERGIRSWDVDPGVCNLDEQLKVF
  VSRHSATFSSIVKGQRSLHHRGDNLETLVLLNPSDKSLYDELRNLLLDPASHKLLVLAGP
  CLEETGELLLQTGGFSPHHFLQVLKDREIRDILATTPPPVQPPILTITCPTFGDWAQLAP
  AVPGLQGALRLQLRLNPPAQLPNSEGLCEFLEYVAESLEPPSPFELLEPPTSGGFLRLGR
  PCCYIFPGGLGDAAFFAVNGFTVLVNGGSNPKSSFWKLVRHLDRVDAVLVTHPGADSLPG
  LNSLLRRKLAERSEVAAGGGSWDDRLRRLISPNLGVVFFNACEAASRLARGEDEAELALS
  LLAQLGITPLPLSRGPVPAKPTVLFEKMGVGRLDMYVLHPPSAGAERTLASVCALLVWHP
  AGPGEKVVRVLFPGCTPPACLLDGLVRLQHLRFLREPVVTPQDLEGPGRAESKESVGSRD
  SSKREGLLATHPRPGQERPGVARKEPARAEAPRKTEKEAKTPRELKKDPKPSVSRTQPRE
  VRRAASSVPNLKKTNAQAAPKPRKAPSTSHSGFPPVANGPRSPPSLRCGEASPPSAACGS
  PASQLVATPSLELGPIPAGEEKALELPLAASSIPRPRTPSPESHRSPAEGSERLSLSPLR
  GGEAGPDASPTVTTPTVTTPSLPAEVGSPHSTEVDESLSVSFEQVLPPSAPTSEAGLSLP
  LRGPRARRSASPHDVDLCLVSPCEFEHRKAVPMAPAPASPGSSNDSSARSQERAGGLGAE
  ETPPTSVSESLPTLSDSDPVPLAPGAADSDEDTEGFGVPRHDPLPDPLKVPPPLPDPSSI
  CMVDPEMLPPKTARQTENVSRTRKPLARPNSRAAAPKATPVAAAKTKGLAGGDRASRPLS
  ARSEPSEKGGRAPLSRKSSTPKTATRGPSGSASSRPGVSATPPKSPVYLDLAYLPSGSSA
  HLVDEEFFQRVRALCYVISGQDQRKEEGMRAVLDALLASKQHWDRDLQVTLIPTFDSVAM
  HTWYAETHARHQALGITVLGSNSMVSMQDDAFPACKVEF
• Function: Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles.
• Tissue Specificity: Expressed in neurons (at protein level). Expressed in spermatocytes, spermatids and spermatozoa. Expressed in the cerebral cortex. Highly expressed in testis. Moderately expressed in the brain, colon, heart, kidney, liver, lung, placenta, small intestine, spleen and stomach. Weakly expressed in muscle.
• KEGG Pathway: Viral life cycle - HIV-1 (hsa03250)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[3]
Giant axonal neuropathy 1	DIS3H1TR	Strong	Biomarker	[4]
Huntington disease	DISQPLA4	Strong	Biomarker	[1]
Kidney failure	DISOVQ9P	Strong	Altered Expression	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[6]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[8]
Liver cancer	DISDE4BI	moderate	Biomarker	[6]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[6]
Prostate cancer	DISF190Y	moderate	Biomarker	[6]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[9]
Breast cancer	DIS7DPX1	Limited	Biomarker	[10]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[10]
Cardiac disease	DISVO1I5	Limited	Genetic Variation	[11]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Parkinson disease	DISQVHKL	Limited	Biomarker	[11]

4 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 Microtubule-associated protein 1S (MAP1S).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microtubule-associated protein 1S (MAP1S).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Microtubule-associated protein 1S (MAP1S).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Microtubule-associated protein 1S (MAP1S).	[22]

10 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 Microtubule-associated protein 1S (MAP1S).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Microtubule-associated protein 1S (MAP1S).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microtubule-associated protein 1S (MAP1S).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Microtubule-associated protein 1S (MAP1S).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule-associated protein 1S (MAP1S).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Microtubule-associated protein 1S (MAP1S).	[18]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Microtubule-associated protein 1S (MAP1S).	[19]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Microtubule-associated protein 1S (MAP1S).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Microtubule-associated protein 1S (MAP1S).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Microtubule-associated protein 1S (MAP1S).	[23]

References

• [1] Blocking the association of HDAC4 with MAP1S accelerates autophagy clearance of mutant Huntingtin.Aging (Albany NY). 2015 Oct;7(10):839-53. doi: 10.18632/aging.100818.
• [2] Overexpression of microRNA-216a inhibits autophagy by targeting regulated MAP1S in colorectal cancer.Onco Targets Ther. 2019 Jun 12;12:4621-4629. doi: 10.2147/OTT.S196992. eCollection 2019.
• [3] Microtubule-associated protein 1S-related autophagy inhibits apoptosis of intestinal epithelial cells via Wnt/-catenin signaling in Crohn's disease.Biochem Biophys Res Commun. 2017 Apr 8;485(3):635-642. doi: 10.1016/j.bbrc.2017.02.034. Epub 2017 Feb 7.
• [4] Gene targeting of GAN in mouse causes a toxic accumulation of microtubule-associated protein 8 and impaired retrograde axonal transport.Hum Mol Genet. 2006 May 1;15(9):1451-63. doi: 10.1093/hmg/ddl069. Epub 2006 Mar 24.
• [5] Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis.Aging (Albany NY). 2016 May;8(5):977-85. doi: 10.18632/aging.100957.
• [6] Transforming Growth Factor TGF Increases Levels of Microtubule-Associated Protein MAP1S and Autophagy Flux in Pancreatic Ductal Adenocarcinomas.PLoS One. 2015 Nov 16;10(11):e0143150. doi: 10.1371/journal.pone.0143150. eCollection 2015.
• [7] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [8] Suppressor of hepatocellular carcinoma RASSF1A activates autophagy initiation and maturation.Cell Death Differ. 2019 Aug;26(8):1379-1395. doi: 10.1038/s41418-018-0211-7. Epub 2018 Oct 12.
• [9] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [10] MAP1S controls breast cancer cell TLR5 signaling pathway and promotes TLR5 signaling-based tumor suppression.PLoS One. 2014 Jan 23;9(1):e86839. doi: 10.1371/journal.pone.0086839. eCollection 2014.
• [11] Microtubule-associated protein 1S (MAP1S) bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation.J Biol Chem. 2011 Mar 25;286(12):10367-77. doi: 10.1074/jbc.M110.206532. Epub 2011 Jan 24.
• [12] 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.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] 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.
• [23] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.